CRKL

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V-crk avian sarcoma virus CT10 oncogene homolog-like
Protein CRKL PDB 2bzx.png
PDB rendering based on 2bzx.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbol CRKL
External IDs OMIM602007 MGI104686 HomoloGene38021 GeneCards: CRKL Gene
RNA expression pattern
PBB GE CRKL 212180 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 1399 12929
Ensembl ENSG00000099942 ENSMUSG00000006134
UniProt P46109 P47941
RefSeq (mRNA) NM_005207 NM_001277231
RefSeq (protein) NP_005198 NP_001264160
Location (UCSC) Chr 22:
20.92 – 20.95 Mb
Chr 16:
17.45 – 17.49 Mb
PubMed search [1] [2]

Crk-like protein is a protein that in humans is encoded by the CRKL gene.[1][2]

Function[edit]

v-CRK avian sarcoma virus CT10-homolog-like contains one SH2 domain and two SH3 domains. CRKL has been shown to activate the RAS and JUN kinase signaling pathways and transform fibroblasts in a RAS-dependent fashion. It is a substrate of the BCR-ABL tyrosine kinase and plays a role in fibroblast transformation by BCR-ABL. In addition, CRKL has oncogenic potential.[3]

CrkL together with Crk participates in the Reelin signaling cascade downstream of DAB1.[4][5]

Interactions[edit]

CRKL has been shown to interact with: CRKL has been shown to interact with:

See also[edit]

References[edit]

  1. ^ ten Hoeve J, Morris C, Heisterkamp N, Groffen J (September 1993). "Isolation and chromosomal localization of CRKL, a human crk-like gene". Oncogene 8 (9): 2469–74. PMID 8361759. 
  2. ^ Senechal K, Halpern J, Sawyers CL (November 1996). "The CRKL adaptor protein transforms fibroblasts and functions in transformation by the BCR-ABL oncogene". J Biol Chem 271 (38): 23255–61. doi:10.1074/jbc.271.38.23255. PMID 8798523. 
  3. ^ "Entrez Gene: CRKL v-crk sarcoma virus CT10 oncogene homolog (avian)-like". 
  4. ^ Matsuki T, Pramatarova A, Howell BW (May 2008). "Reduction of Crk and CrkL expression blocks reelin-induced dendritogenesis". J. Cell. Sci. 121 (Pt 11): 1869–75. doi:10.1242/jcs.027334. PMC 2430739. PMID 18477607. 
  5. ^ Park TJ, Curran T (December 2008). "Crk and crk-like play essential overlapping roles downstream of disabled-1 in the reelin pathway". J. Neurosci. 28 (50): 13551–62. doi:10.1523/JNEUROSCI.4323-08.2008. PMC 2628718. PMID 19074029. 
  6. ^ a b c d Kyono WT, de Jong R, Park RK, Liu Y, Heisterkamp N, Groffen J et al. "Differential interaction of Crkl with Cbl or C3G, Hef-1, and gamma subunit immunoreceptor tyrosine-based activation motif in signaling of myeloid high affinity Fc receptor for IgG (Fc gamma RI)". J. Immunol. 161 (10): 5555–63. PMID 9820532. 
  7. ^ a b Heaney C, Kolibaba K, Bhat A, Oda T, Ohno S, Fanning S et al. "Direct binding of CRKL to BCR-ABL is not required for BCR-ABL transformation". Blood 89 (1): 297–306. PMID 8978305. 
  8. ^ 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. doi:10.1101/gad.8.7.783. PMID 7926767. 
  9. ^ Salgia R, Pisick E, Sattler M, Li JL, Uemura N, Wong WK et al. "p130CAS forms a signaling complex with the adapter protein CRKL in hematopoietic cells transformed by the BCR/ABL oncogene". J. Biol. Chem. 271 (41): 25198–203. doi:10.1074/jbc.271.41.25198. PMID 8810278. 
  10. ^ a b Astier A, Manié SN, Law SF, Canty T, Haghayghi N, Druker BJ et al. "Association of the Cas-like molecule HEF1 with CrkL following integrin and antigen receptor signaling in human B-cells: potential relevance to neoplastic lymphohematopoietic cells". Leuk. Lymphoma 28 (1-2): 65–72. doi:10.3109/10428199709058332. PMID 9498705. 
  11. ^ 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. 
  12. ^ Kolibaba KS, Bhat A, Heaney C, Oda T, Druker BJ. "CRKL binding to BCR-ABL and BCR-ABL transformation". Leuk. Lymphoma 33 (1-2): 119–26. doi:10.3109/10428199909093732. PMID 10194128. 
  13. ^ 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. 
  14. ^ 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. 
  15. ^ van Dijk TB, van Den Akker E, Amelsvoort MP, Mano H, Löwenberg B, von Lindern M. "Stem cell factor induces phosphatidylinositol 3'-kinase-dependent Lyn/Tec/Dok-1 complex formation in hematopoietic cells". Blood 96 (10): 3406–13. PMID 11071635. 
  16. ^ a b c Sattler M, Salgia R, Shrikhande G, Verma S, Pisick E, Prasad KV et al. "Steel factor induces tyrosine phosphorylation of CRKL and binding of CRKL to a complex containing c-kit, phosphatidylinositol 3-kinase, and p120(CBL)". J. Biol. Chem. 272 (15): 10248–53. doi:10.1074/jbc.272.15.10248. PMID 9092574. 
  17. ^ Felschow DM, McVeigh ML, Hoehn GT, Civin CI, Fackler MJ. "The adapter protein CrkL associates with CD34". Blood 97 (12): 3768–75. doi:10.1182/blood.v97.12.3768. PMID 11389015. 
  18. ^ a b c 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. 
  19. ^ Alsayed Y, Modi S, Uddin S, Mahmud N, Druker BJ, Fish EN et al. "All-trans-retinoic acid induces tyrosine phosphorylation of the CrkL adapter in acute promyelocytic leukemia cells". Exp. Hematol. 28 (7): 826–32. doi:10.1016/s0301-472x(00)00170-3. PMID 10907644. 
  20. ^ Lin H, Martelli MP, Bierer BE. "The involvement of the proto-oncogene p120 c-Cbl and ZAP-70 in CD2-mediated T cell activation". Int. Immunol. 13 (1): 13–22. doi:10.1093/intimm/13.1.13. PMID 11133830. 
  21. ^ Park RK, Kyono WT, Liu Y, Durden DL. "CBL-GRB2 interaction in myeloid immunoreceptor tyrosine activation motif signaling". J. Immunol. 160 (10): 5018–27. PMID 9590251. 
  22. ^ Taher TE, Tjin EP, Beuling EA, Borst J, Spaargaren M, Pals ST. "c-Cbl is involved in Met signaling in B cells and mediates hepatocyte growth factor-induced receptor ubiquitination". J. Immunol. 169 (7): 3793–800. doi:10.4049/jimmunol.169.7.3793. PMID 12244174. 
  23. ^ 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. 
  24. ^ a b Sattler M, Salgia R, Shrikhande G, Verma S, Uemura N, Law SF et al. "Differential signaling after beta1 integrin ligation is mediated through binding of CRKL to p120(CBL) and p110(HEF1)". J. Biol. Chem. 272 (22): 14320–6. doi:10.1074/jbc.272.22.14320. PMID 9162067. 
  25. ^ 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. doi:10.1074/jbc.273.7.3986. PMID 9461587. 
  26. ^ Nishihara H, Maeda M, Oda A, Tsuda M, Sawa H, Nagashima K et al. "DOCK2 associates with CrkL and regulates Rac1 in human leukemia cell lines". Blood 100 (12): 3968–74. doi:10.1182/blood-2001-11-0032. PMID 12393632. 
  27. ^ a b Arai A, Kanda E, Nosaka Y, Miyasaka N, Miura O. "CrkL is recruited through its SH2 domain to the erythropoietin receptor and plays a role in Lyn-mediated receptor signaling". J. Biol. Chem. 276 (35): 33282–90. doi:10.1074/jbc.M102924200. PMID 11443118. 
  28. ^ a b Sakkab D, Lewitzky M, Posern G, Schaeper U, Sachs M, Birchmeier W et al. "Signaling of hepatocyte growth factor/scatter factor (HGF) to the small GTPase Rap1 via the large docking protein Gab1 and the adapter protein CRKL". J. Biol. Chem. 275 (15): 10772–8. doi:10.1074/jbc.275.15.10772. PMID 10753869. 
  29. ^ Crouin C, Arnaud M, Gesbert F, Camonis J, Bertoglio J. "A yeast two-hybrid study of human p97/Gab2 interactions with its SH2 domain-containing binding partners". FEBS Lett. 495 (3): 148–53. doi:10.1016/s0014-5793(01)02373-0. PMID 11334882. 
  30. ^ 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. 
  31. ^ 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. 
  32. ^ 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. 
  33. ^ Shi CS, Tuscano J, Kehrl JH. "Adaptor proteins CRK and CRKL associate with the serine/threonine protein kinase GCKR promoting GCKR and SAPK activation". Blood 95 (3): 776–82. PMID 10648385. 
  34. ^ Manié SN, Beck AR, Astier A, Law SF, Canty T, Hirai H et al. "Involvement of p130(Cas) and p105(HEF1), a novel Cas-like docking protein, in a cytoskeleton-dependent signaling pathway initiated by ligation of integrin or antigen receptor on human B cells". J. Biol. Chem. 272 (7): 4230–6. doi:10.1074/jbc.272.7.4230. PMID 9020138. 
  35. ^ Salgia R, Uemura N, Okuda K, Li JL, Pisick E, Sattler M et al. "CRKL links p210BCR/ABL with paxillin in chronic myelogenous leukemia cells". J. Biol. Chem. 270 (49): 29145–50. doi:10.1074/jbc.270.49.29145. PMID 7493940. 
  36. ^ Nishiya N, Tachibana K, Shibanuma M, Mashimo JI, Nose K. "Hic-5-reduced cell spreading on fibronectin: competitive effects between paxillin and Hic-5 through interaction with focal adhesion kinase". Mol. Cell. Biol. 21 (16): 5332–45. doi:10.1128/MCB.21.16.5332-5345.2001. PMC 87257. PMID 11463817. 
  37. ^ Grumbach IM, Mayer IA, Uddin S, Lekmine F, Majchrzak B, Yamauchi H et al. "Engagement of the CrkL adaptor in interferon alpha signalling in BCR-ABL-expressing cells". Br. J. Haematol. 112 (2): 327–36. doi:10.1046/j.1365-2141.2001.02556.x. PMID 11167825. 
  38. ^ Ahmad S, Alsayed YM, Druker BJ, Platanias LC. "The type I interferon receptor mediates tyrosine phosphorylation of the CrkL adaptor protein". J. Biol. Chem. 272 (48): 29991–4. doi:10.1074/jbc.272.48.29991. PMID 9374471. 
  39. ^ 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. doi:10.1074/jbc.271.15.8564. PMID 8621483. 
  40. ^ Wu C, Lai CF, Mobley WC. "Nerve growth factor activates persistent Rap1 signaling in endosomes". J. Neurosci. 21 (15): 5406–16. PMID 11466412. 
  41. ^ Nakamura T, Komiya M, Sone K, Hirose E, Gotoh N, Morii H et al. "Grit, a GTPase-activating protein for the Rho family, regulates neurite extension through association with the TrkA receptor and N-Shc and CrkL/Crk adapter molecules". Mol. Cell. Biol. 22 (24): 8721–34. doi:10.1128/mcb.22.24.8721-8734.2002. PMC 139861. PMID 12446789. 
  42. ^ Ota J, Kimura F, Sato K, Wakimoto N, Nakamura Y, Nagata N et al. "Association of CrkL with STAT5 in hematopoietic cells stimulated by granulocyte-macrophage colony-stimulating factor or erythropoietin". Biochem. Biophys. Res. Commun. 252 (3): 779–86. doi:10.1006/bbrc.1998.9445. PMID 9837784. 
  43. ^ a b Oda A, Ochs HD, Lasky LA, Spencer S, Ozaki K, Fujihara M et al. "CrkL is an adapter for Wiskott-Aldrich syndrome protein and Syk". Blood 97 (9): 2633–9. doi:10.1182/blood.v97.9.2633. PMID 11313252. 

Further reading[edit]

  • Feller SM, Posern G, Voss J, Kardinal C, Sakkab D, Zheng J et al. (1999). "Physiological signals and oncogenesis mediated through Crk family adapter proteins". J. Cell. Physiol. 177 (4): 535–52. doi:10.1002/(SICI)1097-4652(199812)177:4<535::AID-JCP5>3.0.CO;2-E. PMID 10092207. 
  • Salgia R, Uemura N, Okuda K, Li JL, Pisick E, Sattler M et al. (1996). "CRKL links p210BCR/ABL with paxillin in chronic myelogenous leukemia cells". J. Biol. Chem. 270 (49): 29145–50. doi:10.1074/jbc.270.49.29145. PMID 7493940. 
  • Ren R, Ye ZS, Baltimore D (1994). "Abl protein-tyrosine kinase selects the Crk adapter as a substrate using SH3-binding sites". Genes Dev. 8 (7): 783–95. doi:10.1101/gad.8.7.783. PMID 7926767. 
  • Oda T, Heaney C, Hagopian JR, Okuda K, Griffin JD, Druker BJ (1994). "Crkl is the major tyrosine-phosphorylated protein in neutrophils from patients with chronic myelogenous leukemia". J. Biol. Chem. 269 (37): 22925–8. PMID 8083188. 
  • Smit L, van der Horst G, Borst J (1996). "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. doi:10.1074/jbc.271.15.8564. PMID 8621483. 
  • Salgia R, Pisick E, Sattler M, Li JL, Uemura N, Wong WK et al. (1996). "p130CAS forms a signaling complex with the adapter protein CRKL in hematopoietic cells transformed by the BCR/ABL oncogene". J. Biol. Chem. 271 (41): 25198–203. doi:10.1074/jbc.271.41.25198. PMID 8810278. 
  • Ingham RJ, Krebs DL, Barbazuk SM, Turck CW, Hirai H, Matsuda M et al. (1997). "B cell antigen receptor signaling induces the formation of complexes containing the Crk adapter proteins". J. Biol. Chem. 271 (50): 32306–14. doi:10.1074/jbc.271.50.32306. PMID 8943292. 
  • Heaney C, Kolibaba K, Bhat A, Oda T, Ohno S, Fanning S et al. (1997). "Direct binding of CRKL to BCR-ABL is not required for BCR-ABL transformation". Blood 89 (1): 297–306. PMID 8978305. 
  • Manié SN, Beck AR, Astier A, Law SF, Canty T, Hirai H et al. (1997). "Involvement of p130(Cas) and p105(HEF1), a novel Cas-like docking protein, in a cytoskeleton-dependent signaling pathway initiated by ligation of integrin or antigen receptor on human B cells". J. Biol. Chem. 272 (7): 4230–6. doi:10.1074/jbc.272.7.4230. PMID 9020138. 
  • de Jong R, ten Hoeve J, Heisterkamp N, Groffen J (1997). "Tyrosine 207 in CRKL is the BCR/ABL phosphorylation site". Oncogene 14 (5): 507–13. doi:10.1038/sj.onc.1200885. PMID 9053848. 
  • Uemura N, Salgia R, Li JL, Pisick E, Sattler M, Griffin JD (1997). "The BCR/ABL oncogene alters interaction of the adapter proteins CRKL and CRK with cellular proteins". Leukemia 11 (3): 376–85. doi:10.1038/sj.leu.2400590. PMID 9067577. 
  • Sattler M, Salgia R, Shrikhande G, Verma S, Pisick E, Prasad KV et al. (1997). "Steel factor induces tyrosine phosphorylation of CRKL and binding of CRKL to a complex containing c-kit, phosphatidylinositol 3-kinase, and p120(CBL)". J. Biol. Chem. 272 (15): 10248–53. doi:10.1074/jbc.272.15.10248. PMID 9092574. 
  • Sattler M, Salgia R, Shrikhande G, Verma S, Uemura N, Law SF et al. (1997). "Differential signaling after beta1 integrin ligation is mediated through binding of CRKL to p120(CBL) and p110(HEF1)". J. Biol. Chem. 272 (22): 14320–6. doi:10.1074/jbc.272.22.14320. PMID 9162067. 
  • Husson H, Mograbi B, Schmid-Antomarchi H, Fischer S, Rossi B (1997). "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. 
  • Chin H, Saito T, Arai A, Yamamoto K, Kamiyama R, Miyasaka N et al. (1997). "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. 
  • Ahmad S, Alsayed YM, Druker BJ, Platanias LC (1997). "The type I interferon receptor mediates tyrosine phosphorylation of the CrkL adaptor protein". J. Biol. Chem. 272 (48): 29991–4. doi:10.1074/jbc.272.48.29991. PMID 9374471. 
  • de Jong R, van Wijk A, Haataja L, Heisterkamp N, Groffen J (1998). "BCR/ABL-induced leukemogenesis causes phosphorylation of Hef1 and its association with Crkl". J. Biol. Chem. 272 (51): 32649–55. doi:10.1074/jbc.272.51.32649. PMID 9405482. 
  • Gesbert F, Garbay C, Bertoglio J (1998). "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. doi:10.1074/jbc.273.7.3986. PMID 9461587.