GRB2

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Growth factor receptor-bound protein 2
Grb2.JPG
PDB rendering based on 1gri.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols GRB2 ; ASH; EGFRBP-GRB2; Grb3-3; MST084; MSTP084; NCKAP2
External IDs OMIM108355 MGI95805 HomoloGene1576 ChEMBL: 3663 GeneCards: GRB2 Gene
RNA expression pattern
PBB GE GRB2 215075 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 2885 14784
Ensembl ENSG00000177885 ENSMUSG00000059923
UniProt P62993 Q60631
RefSeq (mRNA) NM_002086 NM_008163
RefSeq (protein) NP_002077 NP_032189
Location (UCSC) Chr 17:
73.31 – 73.4 Mb
Chr 11:
115.64 – 115.71 Mb
PubMed search [1] [2]

Growth factor receptor-bound protein 2 also known as Grb2 is an adaptor protein involved in signal transduction/cell communication. In humans, the GRB2 protein is encoded by the GRB2 gene.[1][2]

The protein encoded by this gene binds receptors such as the epidermal growth factor receptor and contains one SH2 domain and two SH3 domains. Its two SH3 domains direct complex formation with proline-rich regions of other proteins, and its SH2 domain binds tyrosine phosphorylated sequences. This gene is similar to the sem-5 gene of Caenorhabditis elegans, which is involved in the signal transduction pathway. Two alternatively spliced transcript variants encoding different isoforms have been found for this gene.[3]

Function and expression[edit]

Grb2 is widely expressed and is essential for multiple cellular functions. Inhibition of Grb2 function impairs developmental processes in various organisms and blocks transformation and proliferation of various cell types, and so it is not surprising that a targeted gene disruption of Grb2 in mouse is lethal at an early embryonic stage. Grb2 is best known for its ability to link the epidermal growth factor receptor tyrosine kinase to the activation of Ras and its downstream kinases, ERK1,2. Grb2 is composed of an SH2 domain flanked on each side by an SH3 domain. Grb2 has two closely related proteins with similar domain organizations, Gads and Grap. Gads and Grap are expressed specifically in hematopoietic cells and function in the coordination of tyrosine kinase mediated signal transduction.

Domains[edit]

The SH2 domain of Grb2 binds to phosphorylated tyrosine-containing peptides on receptors or scaffold proteins with a preference for pY-X-N-X, where X is generally a hydrophobic residue such as valine (see [3]).

The N-terminal SH3 domain binds to proline-rich peptides and can bind to the Ras-guanine exchange factor SOS.

The C-terminal SH3 domain binds to peptides conforming to a P-X-I/L/V/-D/N-R-X-X-K-P motif that allows it to specifically bind to proteins such as Gab-1.[4]

Interactions[edit]

Grb2 has been shown to interact with:

See also[edit]

References[edit]

  1. ^ Matuoka K, Shibata M, Yamakawa A, Takenawa T (October 1992). "Cloning of ASH, a ubiquitous protein composed of one Src homology region (SH) 2 and two SH3 domains, from human and rat cDNA libraries". Proc. Natl. Acad. Sci. U.S.A. 89 (19): 9015–9. doi:10.1073/pnas.89.19.9015. PMC 50055. PMID 1384039. 
  2. ^ a b Lowenstein EJ, Daly RJ, Batzer AG, Li W, Margolis B, Lammers R et al. (August 1992). "The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling". Cell 70 (3): 431–42. doi:10.1016/0092-8674(92)90167-B. PMID 1322798. 
  3. ^ "Entrez Gene: GRB2 growth factor receptor-bound protein 2". 
  4. ^ Berry DM, Nash P, Liu SK, Pawson T, McGlade CJ (2002). "A high-affinity Arg-X-X-Lys SH3 binding motif confers specificity for the interaction between Gads and SLP-76 in T cell signaling". Curr. Biol. 12 (15): 1336–41. doi:10.1016/S0960-9822(02)01038-2. PMID 12176364. 
  5. ^ Poghosyan Z, Robbins SM, Houslay MD, Webster A, Murphy G, Edwards DR. "Phosphorylation-dependent interactions between ADAM15 cytoplasmic domain and Src family protein-tyrosine kinases". J. Biol. Chem. 277 (7): 4999–5007. doi:10.1074/jbc.M107430200. PMID 11741929. 
  6. ^ Warmuth M, Bergmann M, Priess A, Häuslmann K, Emmerich B, Hallek M. "The Src family kinase Hck interacts with Bcr-Abl by a kinase-independent mechanism and phosphorylates the Grb2-binding site of Bcr". J. Biol. Chem. 272 (52): 33260–70. PMID 9407116. 
  7. ^ Ren R, Ye ZS, Baltimore D. "Abl protein-tyrosine kinase selects the Crk adapter as a substrate using SH3-binding sites". Genes Dev. 8 (7): 783–95. PMID 7926767. 
  8. ^ VanderNoot VA, Fitzpatrick FA. "Competitive binding assay of src homology domain 3 interactions between 5-lipoxygenase and growth factor receptor binding protein 2". Anal. Biochem. 230 (1): 108–14. doi:10.1006/abio.1995.1444. PMID 8585605. 
  9. ^ Lepley RA, Fitzpatrick FA. "5-Lipoxygenase contains a functional Src homology 3-binding motif that interacts with the Src homology 3 domain of Grb2 and cytoskeletal proteins". J. Biol. Chem. 269 (39): 24163–8. PMID 7929073. 
  10. ^ Fu C, Turck CW, Kurosaki T, Chan AC. "BLNK: a central linker protein in B cell activation". Immunity 9 (1): 93–103. PMID 9697839. 
  11. ^ Engels N, Wollscheid B, Wienands J. "Association of SLP-65/BLNK with the B cell antigen receptor through a non-ITAM tyrosine of Ig-alpha". Eur. J. Immunol. 31 (7): 2126–34. PMID 11449366. 
  12. ^ Fusaki N, Tomita S, Wu Y, Okamoto N, Goitsuka R, Kitamura D et al. "BLNK is associated with the CD72/SHP-1/Grb2 complex in the WEHI231 cell line after membrane IgM cross-linking". Eur. J. Immunol. 30 (5): 1326–30. PMID 10820378. 
  13. ^ Wienands J, Schweikert J, Wollscheid B, Jumaa H, Nielsen PJ, Reth M. "SLP-65: a new signaling component in B lymphocytes which requires expression of the antigen receptor for phosphorylation". J. Exp. Med. 188 (4): 791–5. PMC 2213353. PMID 9705962. 
  14. ^ a b Angers-Loustau A, Côté JF, Charest A, Dowbenko D, Spencer S, Lasky LA et al. "Protein tyrosine phosphatase-PEST regulates focal adhesion disassembly, migration, and cytokinesis in fibroblasts". J. Cell Biol. 144 (5): 1019–31. PMC 2148201. PMID 10085298. 
  15. ^ Wang X, Weng LP, Yu Q. "Specific inhibition of FGF-induced MAPK activation by the receptor-like protein tyrosine phosphatase LAR". Oncogene 19 (19): 2346–53. doi:10.1038/sj.onc.1203558. PMID 10822386. 
  16. ^ a b c Million RP, Harakawa N, Roumiantsev S, Varticovski L, Van Etten RA. "A direct binding site for Grb2 contributes to transformation and leukemogenesis by the Tel-Abl (ETV6-Abl) tyrosine kinase". Mol. Cell. Biol. 24 (11): 4685–95. doi:10.1128/MCB.24.11.4685-4695.2004. PMC 416425. PMID 15143164. 
  17. ^ a b c Puil L, Liu J, Gish G, Mbamalu G, Bowtell D, Pelicci PG et al. "Bcr-Abl oncoproteins bind directly to activators of the Ras signalling pathway". EMBO J. 13 (4): 764–73. PMC 394874. PMID 8112292. 
  18. ^ Million RP, Van Etten RA. "The Grb2 binding site is required for the induction of chronic myeloid leukemia-like disease in mice by the Bcr/Abl tyrosine kinase". Blood 96 (2): 664–70. PMID 10887132. 
  19. ^ Bai RY, Jahn T, Schrem S, Munzert G, Weidner KM, Wang JY et al. "The SH2-containing adapter protein GRB10 interacts with BCR-ABL". Oncogene 17 (8): 941–8. doi:10.1038/sj.onc.1202024. PMID 9747873. 
  20. ^ Ma G, Lu D, Wu Y, Liu J, Arlinghaus RB. "Bcr phosphorylated on tyrosine 177 binds Grb2". Oncogene 14 (19): 2367–72. doi:10.1038/sj.onc.1201053. PMID 9178913. 
  21. ^ Maru Y, Peters KL, Afar DE, Shibuya M, Witte ON, Smithgall TE. "Tyrosine phosphorylation of BCR by FPS/FES protein-tyrosine kinases induces association of BCR with GRB-2/SOS". Mol. Cell. Biol. 15 (2): 835–42. PMC 231961. PMID 7529874. 
  22. ^ Karoor V, Wang L, Wang HY, Malbon CC. "Insulin stimulates sequestration of beta-adrenergic receptors and enhanced association of beta-adrenergic receptors with Grb2 via tyrosine 350". J. Biol. Chem. 273 (49): 33035–41. PMID 9830057. 
  23. ^ Ponzetto C, Zhen Z, Audero E, Maina F, Bardelli A, Basile ML et al. "Specific uncoupling of GRB2 from the Met receptor. Differential effects on transformation and motility". J. Biol. Chem. 271 (24): 14119–23. PMID 8662889. 
  24. ^ Liang Q, Mohan RR, Chen L, Wilson SE. "Signaling by HGF and KGF in corneal epithelial cells: Ras/MAP kinase and Jak-STAT pathways". Invest. Ophthalmol. Vis. Sci. 39 (8): 1329–38. PMID 9660480. 
  25. ^ a b Ettenberg SA, Keane MM, Nau MM, Frankel M, Wang LM, Pierce JH et al. "cbl-b inhibits epidermal growth factor receptor signaling". Oncogene 18 (10): 1855–66. doi:10.1038/sj.onc.1202499. PMID 10086340. 
  26. ^ Lavagna-Sévenier C, Marchetto S, Birnbaum D, Rosnet O. "The CBL-related protein CBLB participates in FLT3 and interleukin-7 receptor signal transduction in pro-B cells". J. Biol. Chem. 273 (24): 14962–7. PMID 9614102. 
  27. ^ Elly C, Witte S, Zhang Z, Rosnet O, Lipkowitz S, Altman A et al. "Tyrosine phosphorylation and complex formation of Cbl-b upon T cell receptor stimulation". Oncogene 18 (5): 1147–56. doi:10.1038/sj.onc.1202411. PMID 10022120. 
  28. ^ a b Feng GS, Ouyang YB, Hu DP, Shi ZQ, Gentz R, Ni J. "Grap is a novel SH3-SH2-SH3 adaptor protein that couples tyrosine kinases to the Ras pathway". J. Biol. Chem. 271 (21): 12129–32. PMID 8647802. 
  29. ^ De Sepulveda P, Okkenhaug K, Rose JL, Hawley RG, Dubreuil P, Rottapel R. "Socs1 binds to multiple signalling proteins and suppresses steel factor-dependent proliferation". EMBO J. 18 (4): 904–15. doi:10.1093/emboj/18.4.904. PMC 1171183. PMID 10022833. 
  30. ^ Thömmes K, Lennartsson J, Carlberg M, Rönnstrand L. "Identification of Tyr-703 and Tyr-936 as the primary association sites for Grb2 and Grb7 in the c-Kit/stem cell factor receptor". Biochem. J. 341 ( Pt 1): 211–6. PMC 1220349. PMID 10377264. 
  31. ^ Poe JC, Fujimoto M, Jansen PJ, Miller AS, Tedder TF. "CD22 forms a quaternary complex with SHIP, Grb2, and Shc. A pathway for regulation of B lymphocyte antigen receptor-induced calcium flux". J. Biol. Chem. 275 (23): 17420–7. doi:10.1074/jbc.M001892200. PMID 10748054. 
  32. ^ Otipoby KL, Draves KE, Clark EA. "CD22 regulates B cell receptor-mediated signals via two domains that independently recruit Grb2 and SHP-1". J. Biol. Chem. 276 (47): 44315–22. doi:10.1074/jbc.M105446200. PMID 11551923. 
  33. ^ Okkenhaug K, Rottapel R. "Grb2 forms an inducible protein complex with CD28 through a Src homology 3 domain-proline interaction". J. Biol. Chem. 273 (33): 21194–202. PMID 9694876. 
  34. ^ Nunès JA, Truneh A, Olive D, Cantrell DA. "Signal transduction by CD28 costimulatory receptor on T cells. B7-1 and B7-2 regulation of tyrosine kinase adaptor molecules". J. Biol. Chem. 271 (3): 1591–8. PMID 8576157. 
  35. ^ Sugiyama Y, Tomoda K, Tanaka T, Arata Y, Yoneda-Kato N, Kato J. "Direct binding of the signal-transducing adaptor Grb2 facilitates down-regulation of the cyclin-dependent kinase inhibitor p27Kip1". J. Biol. Chem. 276 (15): 12084–90. doi:10.1074/jbc.M010811200. PMID 11278754. 
  36. ^ Riordan SM, Lidder S, Williams R, Skouteris GG. "The beta-subunit of the hepatocyte growth factor/scatter factor (HGF/SF) receptor phosphorylates and associates with CrkII: expression of CrkII enhances HGF/SF-induced mitogenesis". Biochem. J. 350 Pt 3: 925–32. PMC 1221328. PMID 10970810. 
  37. ^ Matsuda M, Ota S, Tanimura R, Nakamura H, Matuoka K, Takenawa T et al. "Interaction between the amino-terminal SH3 domain of CRK and its natural target proteins". J. Biol. Chem. 271 (24): 14468–72. PMID 8662907. 
  38. ^ a b Okada S, Pessin JE. "Interactions between Src homology (SH) 2/SH3 adapter proteins and the guanylnucleotide exchange factor SOS are differentially regulated by insulin and epidermal growth factor". J. Biol. Chem. 271 (41): 25533–8. PMID 8810325. 
  39. ^ a b Erdreich-Epstein A, Liu M, Kant AM, Izadi KD, Nolta JA, Durden DL. "Cbl functions downstream of Src kinases in Fc gamma RI signaling in primary human macrophages". J. Leukoc. Biol. 65 (4): 523–34. PMID 10204582. 
  40. ^ a b c Wong A, Lamothe B, Lee A, Schlessinger J, Lax I, Li A. "FRS2 alpha attenuates FGF receptor signaling by Grb2-mediated recruitment of the ubiquitin ligase Cbl". Proc. Natl. Acad. Sci. U.S.A. 99 (10): 6684–9. doi:10.1073/pnas.052138899. PMC 124463. PMID 11997436. 
  41. ^ a b c d e f Saci A, Liu WQ, Vidal M, Garbay C, Rendu F, Bachelot-Loza C. "Differential effect of the inhibition of Grb2-SH3 interactions in platelet activation induced by thrombin and by Fc receptor engagement". Biochem. J. 363 (Pt 3): 717–25. PMC 1222524. PMID 11964172. 
  42. ^ a b c Liu SK, McGlade CJ. "Gads is a novel SH2 and SH3 domain-containing adaptor protein that binds to tyrosine-phosphorylated Shc". Oncogene 17 (24): 3073–82. doi:10.1038/sj.onc.1202337. PMID 9872323. 
  43. ^ a b c Park RK, Erdreich-Epstein A, Liu M, Izadi KD, Durden DL. "High affinity IgG receptor activation of Src family kinases is required for modulation of the Shc-Grb2-Sos complex and the downstream activation of the nicotinamide adenine dinucleotide phosphate (reduced) oxidase". J. Immunol. 163 (11): 6023–34. PMID 10570290. 
  44. ^ Jain SK, Langdon WY, Varticovski L. "Tyrosine phosphorylation of p120cbl in BCR/abl transformed hematopoietic cells mediates enhanced association with phosphatidylinositol 3-kinase". Oncogene 14 (18): 2217–28. doi:10.1038/sj.onc.1201049. PMID 9174058. 
  45. ^ Robertson H, Langdon WY, Thien CB, Bowtell DD. "A c-Cbl yeast two hybrid screen reveals interactions with 14-3-3 isoforms and cytoskeletal components". Biochem. Biophys. Res. Commun. 240 (1): 46–50. doi:10.1006/bbrc.1997.7608. PMID 9367879. 
  46. ^ Donovan JA, Wange RL, Langdon WY, Samelson LE. "The protein product of the c-cbl protooncogene is the 120-kDa tyrosine-phosphorylated protein in Jurkat cells activated via the T cell antigen receptor". J. Biol. Chem. 269 (37): 22921–4. PMID 8083187. 
  47. ^ Gesbert F, Garbay C, Bertoglio J. "Interleukin-2 stimulation induces tyrosine phosphorylation of p120-Cbl and CrkL and formation of multimolecular signaling complexes in T lymphocytes and natural killer cells". J. Biol. Chem. 273 (7): 3986–93. PMID 9461587. 
  48. ^ Husson H, Mograbi B, Schmid-Antomarchi H, Fischer S, Rossi B. "CSF-1 stimulation induces the formation of a multiprotein complex including CSF-1 receptor, c-Cbl, PI 3-kinase, Crk-II and Grb2". Oncogene 14 (19): 2331–8. doi:10.1038/sj.onc.1201074. PMID 9178909. 
  49. ^ Odai H, Sasaki K, Iwamatsu A, Nakamoto T, Ueno H, Yamagata T et al. "Purification and molecular cloning of SH2- and SH3-containing inositol polyphosphate-5-phosphatase, which is involved in the signaling pathway of granulocyte-macrophage colony-stimulating factor, erythropoietin, and Bcr-Abl". Blood 89 (8): 2745–56. PMID 9108392. 
  50. ^ Ng C, Jackson RA, Buschdorf JP, Sun Q, Guy GR, Sivaraman J. "Structural basis for a novel intrapeptidyl H-bond and reverse binding of c-Cbl-TKB domain substrates". EMBO J. 27 (5): 804–16. doi:10.1038/emboj.2008.18. PMC 2265755. PMID 18273061. 
  51. ^ Mancini A, Niedenthal R, Joos H, Koch A, Trouliaris S, Niemann H et al. "Identification of a second Grb2 binding site in the v-Fms tyrosine kinase". Oncogene 15 (13): 1565–72. doi:10.1038/sj.onc.1201518. PMID 9380408. 
  52. ^ Sahni M, Zhou XM, Bakiri L, Schlessinger J, Baron R, Levy JB. "Identification of a novel 135-kDa Grb2-binding protein in osteoclasts". J. Biol. Chem. 271 (51): 33141–7. PMID 8955163. 
  53. ^ Miki H, Miura K, Matuoka K, Nakata T, Hirokawa N, Orita S et al. "Association of Ash/Grb-2 with dynamin through the Src homology 3 domain". J. Biol. Chem. 269 (8): 5489–92. PMID 8119878. 
  54. ^ a b Sastry L, Cao T, King CR. "Multiple Grb2-protein complexes in human cancer cells". Int. J. Cancer 70 (2): 208–13. PMID 9009162. 
  55. ^ Hsia DA, Mitra SK, Hauck CR, Streblow DN, Nelson JA, Ilic D et al. "Differential regulation of cell motility and invasion by FAK". J. Cell Biol. 160 (5): 753–67. doi:10.1083/jcb.200212114. PMC 2173366. PMID 12615911. 
  56. ^ Hasegawa H, Kiyokawa E, Tanaka S, Nagashima K, Gotoh N, Shibuya M et al. "DOCK180, a major CRK-binding protein, alters cell morphology upon translocation to the cell membrane". Mol. Cell. Biol. 16 (4): 1770–6. PMC 231163. PMID 8657152. 
  57. ^ Yang B, Jung D, Motto D, Meyer J, Koretzky G, Campbell KP. "SH3 domain-mediated interaction of dystroglycan and Grb2". J. Biol. Chem. 270 (20): 11711–4. PMID 7744812. 
  58. ^ Pratt RL, Kinch MS. "Activation of the EphA2 tyrosine kinase stimulates the MAP/ERK kinase signaling cascade". Oncogene 21 (50): 7690–9. doi:10.1038/sj.onc.1205758. PMID 12400011. 
  59. ^ a b c d Oneyama C, Nakano H, Sharma SV. "UCS15A, a novel small molecule, SH3 domain-mediated protein-protein interaction blocking drug". Oncogene 21 (13): 2037–50. doi:10.1038/sj.onc.1205271. PMID 11960376. 
  60. ^ a b c d e Blagoev B, Kratchmarova I, Ong SE, Nielsen M, Foster LJ, Mann M. "A proteomics strategy to elucidate functional protein-protein interactions applied to EGF signaling". Nat. Biotechnol. 21 (3): 315–8. doi:10.1038/nbt790. PMID 12577067. 
  61. ^ a b Schulze WX, Deng L, Mann M. "Phosphotyrosine interactome of the ErbB-receptor kinase family". Mol. Syst. Biol. 1: 2005.0008. doi:10.1038/msb4100012. PMC 1681463. PMID 16729043. 
  62. ^ Wong L, Deb TB, Thompson SA, Wells A, Johnson GR. "A differential requirement for the COOH-terminal region of the epidermal growth factor (EGF) receptor in amphiregulin and EGF mitogenic signaling". J. Biol. Chem. 274 (13): 8900–9. PMID 10085134. 
  63. ^ Okutani T, Okabayashi Y, Kido Y, Sugimoto Y, Sakaguchi K, Matuoka K et al. "Grb2/Ash binds directly to tyrosines 1068 and 1086 and indirectly to tyrosine 1148 of activated human epidermal growth factor receptors in intact cells". J. Biol. Chem. 269 (49): 31310–4. PMID 7527043. 
  64. ^ a b Tortora G, Damiano V, Bianco C, Baldassarre G, Bianco AR, Lanfrancone L et al. "The RIalpha subunit of protein kinase A (PKA) binds to Grb2 and allows PKA interaction with the activated EGF-receptor". Oncogene 14 (8): 923–8. doi:10.1038/sj.onc.1200906. PMID 9050991. 
  65. ^ Daly RJ, Sanderson GM, Janes PW, Sutherland RL. "Cloning and characterization of GRB14, a novel member of the GRB7 gene family". J. Biol. Chem. 271 (21): 12502–10. PMID 8647858. 
  66. ^ a b Buday L, Egan SE, Rodriguez Viciana P, Cantrell DA, Downward J. "A complex of Grb2 adaptor protein, Sos exchange factor, and a 36-kDa membrane-bound tyrosine phosphoprotein is implicated in ras activation in T cells". J. Biol. Chem. 269 (12): 9019–23. PMID 7510700. 
  67. ^ a b Braverman LE, Quilliam LA. "Identification of Grb4/Nckbeta, a src homology 2 and 3 domain-containing adapter protein having similar binding and biological properties to Nck". J. Biol. Chem. 274 (9): 5542–9. PMID 10026169. 
  68. ^ Tauchi T, Feng GS, Shen R, Hoatlin M, Bagby GC, Kabat D et al. "Involvement of SH2-containing phosphotyrosine phosphatase Syp in erythropoietin receptor signal transduction pathways". J. Biol. Chem. 270 (10): 5631–5. PMID 7534299. 
  69. ^ Ong SH, Goh KC, Lim YP, Low BC, Klint P, Claesson-Welsh L et al. "Suc1-associated neurotrophic factor target (SNT) protein is a major FGF-stimulated tyrosine phosphorylated 90-kDa protein which binds to the SH2 domain of GRB2". Biochem. Biophys. Res. Commun. 225 (3): 1021–6. doi:10.1006/bbrc.1996.1288. PMID 8780727. 
  70. ^ Meakin SO, MacDonald JI, Gryz EA, Kubu CJ, Verdi JM. "The signaling adapter FRS-2 competes with Shc for binding to the nerve growth factor receptor TrkA. A model for discriminating proliferation and differentiation". J. Biol. Chem. 274 (14): 9861–70. PMID 10092678. 
  71. ^ Kouhara H, Hadari YR, Spivak-Kroizman T, Schilling J, Bar-Sagi D, Lax I et al. "A lipid-anchored Grb2-binding protein that links FGF-receptor activation to the Ras/MAPK signaling pathway". Cell 89 (5): 693–702. PMID 9182757. 
  72. ^ Ghadimi MP, Sanzenbacher R, Thiede B, Wenzel J, Jing Q, Plomann M et al. "Identification of interaction partners of the cytosolic polyproline region of CD95 ligand (CD178)". FEBS Lett. 519 (1-3): 50–8. PMID 12023017. 
  73. ^ Wenzel J, Sanzenbacher R, Ghadimi M, Lewitzky M, Zhou Q, Kaplan DR et al. "Multiple interactions of the cytosolic polyproline region of the CD95 ligand: hints for the reverse signal transduction capacity of a death factor". FEBS Lett. 509 (2): 255–62. PMID 11741599. 
  74. ^ a b Lewitzky M, Kardinal C, Gehring NH, Schmidt EK, Konkol B, Eulitz M et al. "The C-terminal SH3 domain of the adapter protein Grb2 binds with high affinity to sequences in Gab1 and SLP-76 which lack the SH3-typical P-x-x-P core motif". Oncogene 20 (9): 1052–62. doi:10.1038/sj.onc.1204202. PMID 11314042. 
  75. ^ Holgado-Madruga M, Emlet DR, Moscatello DK, Godwin AK, Wong AJ. "A Grb2-associated docking protein in EGF- and insulin-receptor signalling". Nature 379 (6565): 560–4. doi:10.1038/379560a0. PMID 8596638. 
  76. ^ Lynch DK, Daly RJ. "PKB-mediated negative feedback tightly regulates mitogenic signalling via Gab2". EMBO J. 21 (1-2): 72–82. PMC 125816. PMID 11782427. 
  77. ^ Zhao C, Yu DH, Shen R, Feng GS. "Gab2, a new pleckstrin homology domain-containing adapter protein, acts to uncouple signaling from ERK kinase to Elk-1". J. Biol. Chem. 274 (28): 19649–54. PMID 10391903. 
  78. ^ a b Lee IS, Liu Y, Narazaki M, Hibi M, Kishimoto T, Taga T. "Vav is associated with signal transducing molecules gp130, Grb2 and Erk2, and is tyrosine phosphorylated in response to interleukin-6". FEBS Lett. 401 (2-3): 133–7. PMID 9013873. 
  79. ^ a b Ward AC, Monkhouse JL, Hamilton JA, Csar XF. "Direct binding of Shc, Grb2, SHP-2 and p40 to the murine granulocyte colony-stimulating factor receptor". Biochim. Biophys. Acta 1448 (1): 70–6. PMID 9824671. 
  80. ^ a b Bourguignon LY, Zhu H, Zhou B, Diedrich F, Singleton PA, Hung MC. "Hyaluronan promotes CD44v3-Vav2 interaction with Grb2-p185(HER2) and induces Rac1 and Ras signaling during ovarian tumor cell migration and growth". J. Biol. Chem. 276 (52): 48679–92. doi:10.1074/jbc.M106759200. PMID 11606575. 
  81. ^ Olayioye MA, Graus-Porta D, Beerli RR, Rohrer J, Gay B, Hynes NE. "ErbB-1 and ErbB-2 acquire distinct signaling properties dependent upon their dimerization partner". Mol. Cell. Biol. 18 (9): 5042–51. PMC 109089. PMID 9710588. 
  82. ^ Romero F, Ramos-Morales F, Domínguez A, Rios RM, Schweighoffer F, Tocqué B et al. "Grb2 and its apoptotic isoform Grb3-3 associate with heterogeneous nuclear ribonucleoprotein C, and these interactions are modulated by poly(U) RNA". J. Biol. Chem. 273 (13): 7776–81. PMID 9516488. 
  83. ^ Liu YF, Deth RC, Devys D. "SH3 domain-dependent association of huntingtin with epidermal growth factor receptor signaling complexes". J. Biol. Chem. 272 (13): 8121–4. PMID 9079622. 
  84. ^ Kavanaugh WM, Pot DA, Chin SM, Deuter-Reinhard M, Jefferson AB, Norris FA et al. "Multiple forms of an inositol polyphosphate 5-phosphatase form signaling complexes with Shc and Grb2". Curr. Biol. 6 (4): 438–45. PMID 8723348. 
  85. ^ a b c Giorgetti-Peraldi S, Peyrade F, Baron V, Van Obberghen E. "Involvement of Janus kinases in the insulin signaling pathway". Eur. J. Biochem. 234 (2): 656–60. PMID 8536716. 
  86. ^ a b Skolnik EY, Lee CH, Batzer A, Vicentini LM, Zhou M, Daly R et al. "The SH2/SH3 domain-containing protein GRB2 interacts with tyrosine-phosphorylated IRS1 and Shc: implications for insulin control of ras signalling". EMBO J. 12 (5): 1929–36. PMC 413414. PMID 8491186. 
  87. ^ Morrison KB, Tognon CE, Garnett MJ, Deal C, Sorensen PH. "ETV6-NTRK3 transformation requires insulin-like growth factor 1 receptor signaling and is associated with constitutive IRS-1 tyrosine phosphorylation". Oncogene 21 (37): 5684–95. doi:10.1038/sj.onc.1205669. PMID 12173038. 
  88. ^ Bunnell SC, Diehn M, Yaffe MB, Findell PR, Cantley LC, Berg LJ. "Biochemical interactions integrating Itk with the T cell receptor-initiated signaling cascade". J. Biol. Chem. 275 (3): 2219–30. PMID 10636929. 
  89. ^ Andreotti AH, Bunnell SC, Feng S, Berg LJ, Schreiber SL. "Regulatory intramolecular association in a tyrosine kinase of the Tec family". Nature 385 (6611): 93–7. doi:10.1038/385093a0. PMID 8985255. 
  90. ^ Kim H, Lee YH, Won J, Yun Y. "Through induction of juxtaposition and tyrosine kinase activity of Jak1, X-gene product of hepatitis B virus stimulates Ras and the transcriptional activation through AP-1, NF-kappaB, and SRE enhancers". Biochem. Biophys. Res. Commun. 286 (5): 886–94. doi:10.1006/bbrc.2001.5496. PMID 11527382. 
  91. ^ Chauhan D, Kharbanda SM, Ogata A, Urashima M, Frank D, Malik N et al. "Oncostatin M induces association of Grb2 with Janus kinase JAK2 in multiple myeloma cells". J. Exp. Med. 182 (6): 1801–6. PMC 2192257. PMID 7500025. 
  92. ^ Shen Z, Batzer A, Koehler JA, Polakis P, Schlessinger J, Lydon NB et al. "Evidence for SH3 domain directed binding and phosphorylation of Sam68 by Src". Oncogene 18 (33): 4647–53. doi:10.1038/sj.onc.1203079. PMID 10467411. 
  93. ^ Paz PE, Wang S, Clarke H, Lu X, Stokoe D, Abo A. "Mapping the Zap-70 phosphorylation sites on LAT (linker for activation of T cells) required for recruitment and activation of signalling proteins in T cells". Biochem. J. 356 (Pt 2): 461–71. PMC 1221857. PMID 11368773. 
  94. ^ Zhang W, Sloan-Lancaster J, Kitchen J, Trible RP, Samelson LE. "LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation". Cell 92 (1): 83–92. PMID 9489702. 
  95. ^ Perez-Villar JJ, Whitney GS, Sitnick MT, Dunn RJ, Venkatesan S, O'Day K et al. "Phosphorylation of the linker for activation of T-cells by Itk promotes recruitment of Vav". Biochemistry 41 (34): 10732–40. PMID 12186560. 
  96. ^ a b Robinson A, Gibbins J, Rodríguez-Liñares B, Finan PM, Wilson L, Kellie S et al. "Characterization of Grb2-binding proteins in human platelets activated by Fc gamma RIIA cross-linking". Blood 88 (2): 522–30. PMID 8695800. 
  97. ^ Hendricks-Taylor LR, Motto DG, Zhang J, Siraganian RP, Koretzky GA. "SLP-76 is a substrate of the high affinity IgE receptor-stimulated protein tyrosine kinases in rat basophilic leukemia cells". J. Biol. Chem. 272 (2): 1363–7. PMID 8995445. 
  98. ^ Asada H, Ishii N, Sasaki Y, Endo K, Kasai H, Tanaka N et al. "Grf40, A novel Grb2 family member, is involved in T cell signaling through interaction with SLP-76 and LAT". J. Exp. Med. 189 (9): 1383–90. PMC 2193052. PMID 10224278. 
  99. ^ Lim RW, Halpain S. "Regulated association of microtubule-associated protein 2 (MAP2) with Src and Grb2: evidence for MAP2 as a scaffolding protein". J. Biol. Chem. 275 (27): 20578–87. doi:10.1074/jbc.M001887200. PMID 10781592. 
  100. ^ Zamora-Leon SP, Lee G, Davies P, Shafit-Zagardo B. "Binding of Fyn to MAP-2c through an SH3 binding domain. Regulation of the interaction by ERK2". J. Biol. Chem. 276 (43): 39950–8. doi:10.1074/jbc.M107807200. PMID 11546790. 
  101. ^ Pomérance M, Multon MC, Parker F, Venot C, Blondeau JP, Tocqué B et al. "Grb2 interaction with MEK-kinase 1 is involved in regulation of Jun-kinase activities in response to epidermal growth factor". J. Biol. Chem. 273 (38): 24301–4. PMID 9733714. 
  102. ^ Oehrl W, Kardinal C, Ruf S, Adermann K, Groffen J, Feng GS et al. "The germinal center kinase (GCK)-related protein kinases HPK1 and KHS are candidates for highly selective signal transducers of Crk family adapter proteins". Oncogene 17 (15): 1893–901. doi:10.1038/sj.onc.1202108. PMID 9788432. 
  103. ^ Anafi M, Kiefer F, Gish GD, Mbamalu G, Iscove NN, Pawson T. "SH2/SH3 adaptor proteins can link tyrosine kinases to a Ste20-related protein kinase, HPK1". J. Biol. Chem. 272 (44): 27804–11. PMID 9346925. 
  104. ^ Ling P, Yao Z, Meyer CF, Wang XS, Oehrl W, Feller SM et al. "Interaction of hematopoietic progenitor kinase 1 with adapter proteins Crk and CrkL leads to synergistic activation of c-Jun N-terminal kinase". Mol. Cell. Biol. 19 (2): 1359–68. PMC 116064. PMID 9891069. 
  105. ^ Ling P, Meyer CF, Redmond LP, Shui JW, Davis B, Rich RR et al. "Involvement of hematopoietic progenitor kinase 1 in T cell receptor signaling". J. Biol. Chem. 276 (22): 18908–14. doi:10.1074/jbc.M101485200. PMID 11279207. 
  106. ^ Wiederhold T, Lee MF, James M, Neujahr R, Smith N, Murthy A et al. "Magicin, a novel cytoskeletal protein associates with the NF2 tumor suppressor merlin and Grb2". Oncogene 23 (54): 8815–25. doi:10.1038/sj.onc.1208110. PMID 15467741. 
  107. ^ Li BQ, Wang MH, Kung HF, Ronsin C, Breathnach R, Leonard EJ et al. "Macrophage-stimulating protein activates Ras by both activation and translocation of SOS nucleotide exchange factor". Biochem. Biophys. Res. Commun. 216 (1): 110–8. doi:10.1006/bbrc.1995.2598. PMID 7488076. 
  108. ^ Iwama A, Yamaguchi N, Suda T. "STK/RON receptor tyrosine kinase mediates both apoptotic and growth signals via the multifunctional docking site conserved among the HGF receptor family". EMBO J. 15 (21): 5866–75. PMC 452340. PMID 8918464. 
  109. ^ a b Pandey P, Kharbanda S, Kufe D. "Association of the DF3/MUC1 breast cancer antigen with Grb2 and the Sos/Ras exchange protein". Cancer Res. 55 (18): 4000–3. PMID 7664271. 
  110. ^ Saleem A, Datta R, Yuan ZM, Kharbanda S, Kufe D. "Involvement of stress-activated protein kinase in the cellular response to 1-beta-D-arabinofuranosylcytosine and other DNA-damaging agents". Cell Growth Differ. 6 (12): 1651–8. PMID 9019171. 
  111. ^ Kharbanda S, Saleem A, Shafman T, Emoto Y, Taneja N, Rubin E et al. "Ionizing radiation stimulates a Grb2-mediated association of the stress-activated protein kinase with phosphatidylinositol 3-kinase". J. Biol. Chem. 270 (32): 18871–4. PMID 7642542. 
  112. ^ Satoh S, Tominaga T. "mDia-interacting protein acts downstream of Rho-mDia and modifies Src activation and stress fiber formation". J. Biol. Chem. 276 (42): 39290–4. doi:10.1074/jbc.M107026200. PMID 11509578. 
  113. ^ Fukuoka M, Suetsugu S, Miki H, Fukami K, Endo T, Takenawa T. "A novel neural Wiskott-Aldrich syndrome protein (N-WASP) binding protein, WISH, induces Arp2/3 complex activation independent of Cdc42". J. Cell Biol. 152 (3): 471–82. PMC 2196001. PMID 11157975. 
  114. ^ Sasaki A, Hata K, Suzuki S, Sawada M, Wada T, Yamaguchi K et al. "Overexpression of plasma membrane-associated sialidase attenuates insulin signaling in transgenic mice". J. Biol. Chem. 278 (30): 27896–902. doi:10.1074/jbc.M212200200. PMID 12730204. 
  115. ^ Arvidsson AK, Rupp E, Nånberg E, Downward J, Rönnstrand L, Wennström S et al. "Tyr-716 in the platelet-derived growth factor beta-receptor kinase insert is involved in GRB2 binding and Ras activation". Mol. Cell. Biol. 14 (10): 6715–26. PMC 359202. PMID 7935391. 
  116. ^ a b Tang J, Feng GS, Li W. "Induced direct binding of the adapter protein Nck to the GTPase-activating protein-associated protein p62 by epidermal growth factor". Oncogene 15 (15): 1823–32. doi:10.1038/sj.onc.1201351. PMID 9362449. 
  117. ^ Saleem A, Kharbanda S, Yuan ZM, Kufe D. "Monocyte colony-stimulating factor stimulates binding of phosphatidylinositol 3-kinase to Grb2.Sos complexes in human monocytes". J. Biol. Chem. 270 (18): 10380–3. PMID 7737969. 
  118. ^ Wang J, Auger KR, Jarvis L, Shi Y, Roberts TM. "Direct association of Grb2 with the p85 subunit of phosphatidylinositol 3-kinase". J. Biol. Chem. 270 (21): 12774–80. PMID 7759531. 
  119. ^ Pei Z, Maloney JA, Yang L, Williamson JR. "A new function for phospholipase C-gamma1: coupling to the adaptor protein GRB2". Arch. Biochem. Biophys. 345 (1): 103–10. doi:10.1006/abbi.1997.0245. PMID 9281317. 
  120. ^ a b Nel AE, Gupta S, Lee L, Ledbetter JA, Kanner SB. "Ligation of the T-cell antigen receptor (TCR) induces association of hSos1, ZAP-70, phospholipase C-gamma 1, and other phosphoproteins with Grb2 and the zeta-chain of the TCR". J. Biol. Chem. 270 (31): 18428–36. PMID 7629168. 
  121. ^ Scholler JK, Perez-Villar JJ, O'Day K, Kanner SB. "Engagement of the T lymphocyte antigen receptor regulates association of son-of-sevenless homologues with the SH3 domain of phospholipase Cgamma1". Eur. J. Immunol. 30 (8): 2378–87. doi:10.1002/1521-4141(2000)30:8<2378::AID-IMMU2378>3.0.CO;2-E. PMID 10940929. 
  122. ^ Sieg DJ, Hauck CR, Ilic D, Klingbeil CK, Schaefer E, Damsky CH et al. "FAK integrates growth-factor and integrin signals to promote cell migration". Nat. Cell Biol. 2 (5): 249–56. doi:10.1038/35010517. PMID 10806474. 
  123. ^ Hildebrand JD, Taylor JM, Parsons JT. "An SH3 domain-containing GTPase-activating protein for Rho and Cdc42 associates with focal adhesion kinase". Mol. Cell. Biol. 16 (6): 3169–78. PMC 231310. PMID 8649427. 
  124. ^ Messina S, Onofri F, Bongiorno-Borbone L, Giovedì S, Valtorta F, Girault JA et al. "Specific interactions of neuronal focal adhesion kinase isoforms with Src kinases and amphiphysin". J. Neurochem. 84 (2): 253–65. PMID 12558988. 
  125. ^ Arold ST, Hoellerer MK, Noble ME. "The structural basis of localization and signaling by the focal adhesion targeting domain". Structure 10 (3): 319–27. PMID 12005431. 
  126. ^ a b Zhang S, Mantel C, Broxmeyer HE. "Flt3 signaling involves tyrosyl-phosphorylation of SHP-2 and SHIP and their association with Grb2 and Shc in Baf3/Flt3 cells". J. Leukoc. Biol. 65 (3): 372–80. PMID 10080542. 
  127. ^ a b c Ganju RK, Brubaker SA, Chernock RD, Avraham S, Groopman JE. "Beta-chemokine receptor CCR5 signals through SHP1, SHP2, and Syk". J. Biol. Chem. 275 (23): 17263–8. doi:10.1074/jbc.M000689200. PMID 10747947. 
  128. ^ Bennett AM, Tang TL, Sugimoto S, Walsh CT, Neel BG. "Protein-tyrosine-phosphatase SHPTP2 couples platelet-derived growth factor receptor beta to Ras". Proc. Natl. Acad. Sci. U.S.A. 91 (15): 7335–9. PMC 44394. PMID 8041791. 
  129. ^ Yin T, Shen R, Feng GS, Yang YC. "Molecular characterization of specific interactions between SHP-2 phosphatase and JAK tyrosine kinases". J. Biol. Chem. 272 (2): 1032–7. PMID 8995399. 
  130. ^ Tang H, Zhao ZJ, Huang XY, Landon EJ, Inagami T. "Fyn kinase-directed activation of SH2 domain-containing protein-tyrosine phosphatase SHP-2 by Gi protein-coupled receptors in Madin-Darby canine kidney cells". J. Biol. Chem. 274 (18): 12401–7. PMID 10212213. 
  131. ^ Hadari YR, Kouhara H, Lax I, Schlessinger J. "Binding of Shp2 tyrosine phosphatase to FRS2 is essential for fibroblast growth factor-induced PC12 cell differentiation". Mol. Cell. Biol. 18 (7): 3966–73. PMC 108981. PMID 9632781. 
  132. ^ Wong L, Johnson GR. "Epidermal growth factor induces coupling of protein-tyrosine phosphatase 1D to GRB2 via the COOH-terminal SH3 domain of GRB2". J. Biol. Chem. 271 (35): 20981–4. PMID 8702859. 
  133. ^ Charest A, Wagner J, Kwan M, Tremblay ML. "Coupling of the murine protein tyrosine phosphatase PEST to the epidermal growth factor (EGF) receptor through a Src homology 3 (SH3) domain-mediated association with Grb2". Oncogene 14 (14): 1643–51. doi:10.1038/sj.onc.1201008. PMID 9135065. 
  134. ^ Goldstein BJ, Bittner-Kowalczyk A, White MF, Harbeck M. "Tyrosine dephosphorylation and deactivation of insulin receptor substrate-1 by protein-tyrosine phosphatase 1B. Possible facilitation by the formation of a ternary complex with the Grb2 adaptor protein". J. Biol. Chem. 275 (6): 4283–9. PMID 10660596. 
  135. ^ Liu F, Hill DE, Chernoff J. "Direct binding of the proline-rich region of protein tyrosine phosphatase 1B to the Src homology 3 domain of p130(Cas)". J. Biol. Chem. 271 (49): 31290–5. PMID 8940134. 
  136. ^ Kon-Kozlowski M, Pani G, Pawson T, Siminovitch KA. "The tyrosine phosphatase PTP1C associates with Vav, Grb2, and mSos1 in hematopoietic cells". J. Biol. Chem. 271 (7): 3856–62. PMID 8632004. 
  137. ^ den Hertog J, Hunter T. "Tight association of GRB2 with receptor protein-tyrosine phosphatase alpha is mediated by the SH2 and C-terminal SH3 domains". EMBO J. 15 (12): 3016–27. PMC 450243. PMID 8670803. 
  138. ^ den Hertog J, Tracy S, Hunter T. "Phosphorylation of receptor protein-tyrosine phosphatase alpha on Tyr789, a binding site for the SH3-SH2-SH3 adaptor protein GRB-2 in vivo". EMBO J. 13 (13): 3020–32. PMC 395191. PMID 7518772. 
  139. ^ Zheng XM, Resnick RJ, Shalloway D. "Mitotic activation of protein-tyrosine phosphatase alpha and regulation of its Src-mediated transforming activity by its sites of protein kinase C phosphorylation". J. Biol. Chem. 277 (24): 21922–9. doi:10.1074/jbc.M201394200. PMID 11923305. 
  140. ^ Smit L, van der Horst G, Borst J. "Sos, Vav, and C3G participate in B cell receptor-induced signaling pathways and differentially associate with Shc-Grb2, Crk, and Crk-L adaptors". J. Biol. Chem. 271 (15): 8564–9. PMID 8621483. 
  141. ^ Tanaka S, Morishita T, Hashimoto Y, Hattori S, Nakamura S, Shibuya M et al. "C3G, a guanine nucleotide-releasing protein expressed ubiquitously, binds to the Src homology 3 domains of CRK and GRB2/ASH proteins". Proc. Natl. Acad. Sci. U.S.A. 91 (8): 3443–7. PMC 43593. PMID 7512734. 
  142. ^ Borrello MG, Pelicci G, Arighi E, De Filippis L, Greco A, Bongarzone I et al. "The oncogenic versions of the Ret and Trk tyrosine kinases bind Shc and Grb2 adaptor proteins". Oncogene 9 (6): 1661–8. PMID 8183561. 
  143. ^ Pandey A, Duan H, Di Fiore PP, Dixit VM. "The Ret receptor protein tyrosine kinase associates with the SH2-containing adapter protein Grb10". J. Biol. Chem. 270 (37): 21461–3. PMID 7665556. 
  144. ^ Qian X, Riccio A, Zhang Y, Ginty DD. "Identification and characterization of novel substrates of Trk receptors in developing neurons". Neuron 21 (5): 1017–29. PMID 9856458. 
  145. ^ Kotani K, Wilden P, Pillay TS. "SH2-Balpha is an insulin-receptor adapter protein and substrate that interacts with the activation loop of the insulin-receptor kinase". Biochem. J. 335 ( Pt 1): 103–9. PMC 1219757. PMID 9742218. 
  146. ^ Gout I, Middleton G, Adu J, Ninkina NN, Drobot LB, Filonenko V et al. "Negative regulation of PI 3-kinase by Ruk, a novel adaptor protein". EMBO J. 19 (15): 4015–25. doi:10.1093/emboj/19.15.4015. PMC 306608. PMID 10921882. 
  147. ^ Borinstein SC, Hyatt MA, Sykes VW, Straub RE, Lipkowitz S, Boulter J et al. "SETA is a multifunctional adapter protein with three SH3 domains that binds Grb2, Cbl, and the novel SB1 proteins". Cell. Signal. 12 (11-12): 769–79. PMID 11152963. 
  148. ^ a b Satoh T, Kato J, Nishida K, Kaziro Y. "Tyrosine phosphorylation of ACK in response to temperature shift-down, hyperosmotic shock, and epidermal growth factor stimulation". FEBS Lett. 386 (2-3): 230–4. PMID 8647288. 
  149. ^ Fixman ED, Fournier TM, Kamikura DM, Naujokas MA, Park M. "Pathways downstream of Shc and Grb2 are required for cell transformation by the tpr-Met oncoprotein". J. Biol. Chem. 271 (22): 13116–22. PMID 8662733. 
  150. ^ Ishihara H, Sasaoka T, Ishiki M, Takata Y, Imamura T, Usui I et al. "Functional importance of Shc tyrosine 317 on insulin signaling in Rat1 fibroblasts expressing insulin receptors". J. Biol. Chem. 272 (14): 9581–6. PMID 9083103. 
  151. ^ Fournier E, Blaikie P, Rosnet O, Margolis B, Birnbaum D, Borg JP. "Role of tyrosine residues and protein interaction domains of SHC adaptor in VEGF receptor 3 signaling". Oncogene 18 (2): 507–14. doi:10.1038/sj.onc.1202315. PMID 9927207. 
  152. ^ Ravichandran KS, Burakoff SJ. "The adapter protein Shc interacts with the interleukin-2 (IL-2) receptor upon IL-2 stimulation". J. Biol. Chem. 269 (3): 1599–602. PMID 8294403. 
  153. ^ Lamprecht R, Farb CR, LeDoux JE. "Fear memory formation involves p190 RhoGAP and ROCK proteins through a GRB2-mediated complex". Neuron 36 (4): 727–38. PMID 12441060. 
  154. ^ a b Park RK, Izadi KD, Deo YM, Durden DL. "Role of Src in the modulation of multiple adaptor proteins in FcalphaRI oxidant signaling". Blood 94 (6): 2112–20. PMID 10477741. 
  155. ^ Sakaguchi K, Okabayashi Y, Kasuga M. "Shc mediates ligand-induced internalization of epidermal growth factor receptors". Biochem. Biophys. Res. Commun. 282 (5): 1154–60. doi:10.1006/bbrc.2001.4680. PMID 11302736. 
  156. ^ Hallak H, Seiler AE, Green JS, Henderson A, Ross BN, Rubin R. "Inhibition of insulin-like growth factor-I signaling by ethanol in neuronal cells". Alcohol. Clin. Exp. Res. 25 (7): 1058–64. PMID 11505033. 
  157. ^ Yokote K, Mori S, Hansen K, McGlade J, Pawson T, Heldin CH et al. "Direct interaction between Shc and the platelet-derived growth factor beta-receptor". J. Biol. Chem. 269 (21): 15337–43. PMID 8195171. 
  158. ^ Lazar DF, Knez JJ, Medof ME, Cuatrecasas P, Saltiel AR. "Stimulation of glycogen synthesis by insulin in human erythroleukemia cells requires the synthesis of glycosyl-phosphatidylinositol". Proc. Natl. Acad. Sci. U.S.A. 91 (21): 9665–9. PMC 44877. PMID 7524086. 
  159. ^ VanderKuur J, Allevato G, Billestrup N, Norstedt G, Carter-Su C. "Growth hormone-promoted tyrosyl phosphorylation of SHC proteins and SHC association with Grb2". J. Biol. Chem. 270 (13): 7587–93. PMID 7535773. 
  160. ^ Kanai M, Göke M, Tsunekawa S, Podolsky DK. "Signal transduction pathway of human fibroblast growth factor receptor 3. Identification of a novel 66-kDa phosphoprotein". J. Biol. Chem. 272 (10): 6621–8. PMID 9045692. 
  161. ^ a b Spivak-Kroizman T, Mohammadi M, Hu P, Jaye M, Schlessinger J, Lax I. "Point mutation in the fibroblast growth factor receptor eliminates phosphatidylinositol hydrolysis without affecting neuronal differentiation of PC12 cells". J. Biol. Chem. 269 (20): 14419–23. PMID 7514169. 
  162. ^ Giordano V, De Falco G, Chiari R, Quinto I, Pelicci PG, Bartholomew L et al. "Shc mediates IL-6 signaling by interacting with gp130 and Jak2 kinase". J. Immunol. 158 (9): 4097–103. PMID 9126968. 
  163. ^ a b Germani A, Romero F, Houlard M, Camonis J, Gisselbrecht S, Fischer S et al. "hSiah2 is a new Vav binding protein which inhibits Vav-mediated signaling pathways". Mol. Cell. Biol. 19 (5): 3798–807. PMC 84217. PMID 10207103. 
  164. ^ Li N, Batzer A, Daly R, Yajnik V, Skolnik E, Chardin P et al. "Guanine-nucleotide-releasing factor hSos1 binds to Grb2 and links receptor tyrosine kinases to Ras signalling". Nature 363 (6424): 85–8. doi:10.1038/363085a0. PMID 8479541. 
  165. ^ Reif K, Buday L, Downward J, Cantrell DA. "SH3 domains of the adapter molecule Grb2 complex with two proteins in T cells: the guanine nucleotide exchange protein Sos and a 75-kDa protein that is a substrate for T cell antigen receptor-activated tyrosine kinases". J. Biol. Chem. 269 (19): 14081–7. PMID 8188688. 
  166. ^ D'Angelo G, Martini JF, Iiri T, Fantl WJ, Martial J, Weiner RI. "16K human prolactin inhibits vascular endothelial growth factor-induced activation of Ras in capillary endothelial cells". Mol. Endocrinol. 13 (5): 692–704. doi:10.1210/mend.13.5.0280. PMID 10319320. 
  167. ^ Tong XK, Hussain NK, de Heuvel E, Kurakin A, Abi-Jaoude E, Quinn CC et al. "The endocytic protein intersectin is a major binding partner for the Ras exchange factor mSos1 in rat brain". EMBO J. 19 (6): 1263–71. doi:10.1093/emboj/19.6.1263. PMC 305667. PMID 10716926. 
  168. ^ Chin H, Saito T, Arai A, Yamamoto K, Kamiyama R, Miyasaka N et al. "Erythropoietin and IL-3 induce tyrosine phosphorylation of CrkL and its association with Shc, SHP-2, and Cbl in hematopoietic cells". Biochem. Biophys. Res. Commun. 239 (2): 412–7. doi:10.1006/bbrc.1997.7480. PMID 9344843. 
  169. ^ Wan KF, Sambi BS, Tate R, Waters C, Pyne NJ. "The inhibitory gamma subunit of the type 6 retinal cGMP phosphodiesterase functions to link c-Src and G-protein-coupled receptor kinase 2 in a signaling unit that regulates p42/p44 mitogen-activated protein kinase by epidermal growth factor". J. Biol. Chem. 278 (20): 18658–63. doi:10.1074/jbc.M212103200. PMID 12624098. 
  170. ^ Kato-Stankiewicz J, Ueda S, Kataoka T, Kaziro Y, Satoh T. "Epidermal growth factor stimulation of the ACK1/Dbl pathway in a Cdc42 and Grb2-dependent manner". Biochem. Biophys. Res. Commun. 284 (2): 470–7. doi:10.1006/bbrc.2001.5004. PMID 11394904. 
  171. ^ Song C, Perides G, Liu YF. "Expression of full-length polyglutamine-expanded Huntingtin disrupts growth factor receptor signaling in rat pheochromocytoma (PC12) cells". J. Biol. Chem. 277 (8): 6703–7. doi:10.1074/jbc.M110338200. PMID 11733534. 
  172. ^ MacDonald JI, Gryz EA, Kubu CJ, Verdi JM, Meakin SO. "Direct binding of the signaling adapter protein Grb2 to the activation loop tyrosines on the nerve growth factor receptor tyrosine kinase, TrkA". J. Biol. Chem. 275 (24): 18225–33. doi:10.1074/jbc.M001862200. PMID 10748052. 
  173. ^ Song JS, Gomez J, Stancato LF, Rivera J. "Association of a p95 Vav-containing signaling complex with the FcepsilonRI gamma chain in the RBL-2H3 mast cell line. Evidence for a constitutive in vivo association of Vav with Grb2, Raf-1, and ERK2 in an active complex". J. Biol. Chem. 271 (43): 26962–70. PMID 8900182. 
  174. ^ Ye ZS, Baltimore D. "Binding of Vav to Grb2 through dimerization of Src homology 3 domains". Proc. Natl. Acad. Sci. U.S.A. 91 (26): 12629–33. PMC 45492. PMID 7809090. 
  175. ^ Zeng L, Sachdev P, Yan L, Chan JL, Trenkle T, McClelland M et al. "Vav3 mediates receptor protein tyrosine kinase signaling, regulates GTPase activity, modulates cell morphology, and induces cell transformation". Mol. Cell. Biol. 20 (24): 9212–24. PMC 102179. PMID 11094073. 
  176. ^ Banin S, Truong O, Katz DR, Waterfield MD, Brickell PM, Gout I. "Wiskott-Aldrich syndrome protein (WASp) is a binding partner for c-Src family protein-tyrosine kinases". Curr. Biol. 6 (8): 981–8. PMID 8805332. 
  177. ^ She HY, Rockow S, Tang J, Nishimura R, Skolnik EY, Chen M et al. "Wiskott-Aldrich syndrome protein is associated with the adapter protein Grb2 and the epidermal growth factor receptor in living cells". Mol. Biol. Cell 8 (9): 1709–21. PMC 305731. PMID 9307968. 

Further reading[edit]

  • Colledge M, Froehner SC (1998). "Interaction between the nicotinic acetylcholine receptor and Grb2. Implications for signaling at the neuromuscular junction.". Ann. N. Y. Acad. Sci. 841: 17–27. doi:10.1111/j.1749-6632.1998.tb10907.x. PMID 9668219. 
  • Ramesh N, Antón IM, Martínez-Quiles N, Geha RS (1999). "Waltzing with WASP.". Trends Cell Biol. 9 (1): 15–9. doi:10.1016/S0962-8924(98)01411-1. PMID 10087612. 
  • O'Sullivan E, Kinnon C, Brickell P (1999). "Wiskott-Aldrich syndrome protein, WASP.". Int. J. Biochem. Cell Biol. 31 (3–4): 383–7. doi:10.1016/S1357-2725(98)00118-6. PMID 10224664. 
  • Schlaepfer DD, Hauck CR, Sieg DJ (1999). "Signaling through focal adhesion kinase.". Prog. Biophys. Mol. Biol. 71 (3–4): 435–78. doi:10.1016/S0079-6107(98)00052-2. PMID 10354709. 
  • Vidal M, Liu WQ, Gril B, Assayag F, Poupon MF, Garbay C (2004). "[Design of new anti-tumor agents interrupting deregulated signaling pathways induced by tyrosine kinase proteins. Inhibition of protein-protein interaction involving Grb2]". J. Soc. Biol. 198 (2): 133–7. PMID 15368963. 

External links[edit]