CRKL

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V-crk sarcoma virus CT10 oncogene homolog (avian)-like

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:
21.27 – 21.31 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]

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:

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. ^ Crouin, C; Arnaud M, Gesbert F, Camonis J, Bertoglio J (April 2001). "A yeast two-hybrid study of human p97/Gab2 interactions with its SH2 domain-containing binding partners". FEBS Lett. (Netherlands) 495 (3): 148–53. doi:10.1016/S0014-5793(01)02373-0. ISSN 0014-5793. PMID 11334882. 
  7. ^ Felschow, D M; McVeigh M L, Hoehn G T, Civin C I, Fackler M J (June 2001). "The adapter protein CrkL associates with CD34". Blood (United States) 97 (12): 3768–75. doi:10.1182/blood.V97.12.3768. ISSN 0006-4971. PMID 11389015. 
  8. ^ van Dijk, T B; van Den Akker E, Amelsvoort M P, Mano H, Löwenberg B, von Lindern M (November 2000). "Stem cell factor induces phosphatidylinositol 3'-kinase-dependent Lyn/Tec/Dok-1 complex formation in hematopoietic cells". Blood (UNITED STATES) 96 (10): 3406–13. ISSN 0006-4971. PMID 11071635. 
  9. ^ a b c Sattler, M; Salgia R, Shrikhande G, Verma S, Pisick E, Prasad K V, Griffin J D (April 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. (UNITED STATES) 272 (15): 10248–53. doi:10.1074/jbc.272.15.10248. ISSN 0021-9258. PMID 9092574. 
  10. ^ Shi, C S; Tuscano J, Kehrl J H (February 2000). "Adaptor proteins CRK and CRKL associate with the serine/threonine protein kinase GCKR promoting GCKR and SAPK activation". Blood (UNITED STATES) 95 (3): 776–82. ISSN 0006-4971. PMID 10648385. 
  11. ^ Oehrl, W; Kardinal C, Ruf S, Adermann K, Groffen J, Feng G S, Blenis J, Tan T H, Feller S M (October 1998). "The germinal center kinase (GCK)-related protein kinases HPK1 and KHS are candidates for highly selective signal transducers of Crk family adapter proteins". Oncogene (ENGLAND) 17 (15): 1893–901. doi:10.1038/sj.onc.1202108. ISSN 0950-9232. PMID 9788432. 
  12. ^ Ling, P; Yao Z, Meyer C F, Wang X S, Oehrl W, Feller S M, Tan T H (February 1999). "Interaction of hematopoietic progenitor kinase 1 with adapter proteins Crk and CrkL leads to synergistic activation of c-June N-terminal kinase". Mol. Cell. Biol. (UNITED STATES) 19 (2): 1359–68. ISSN 0270-7306. PMC 116064. PMID 9891069. 
  13. ^ Ling, P; Meyer C F, Redmond L P, Shui J W, Davis B, Rich R R, Hu M C, Wange R L, Tan T H (June 2001). "Involvement of hematopoietic progenitor kinase 1 in T cell receptor signaling". J. Biol. Chem. (United States) 276 (22): 18908–14. doi:10.1074/jbc.M101485200. ISSN 0021-9258. PMID 11279207. 
  14. ^ a b Oda, A; Ochs H D, Lasky L A, Spencer S, Ozaki K, Fujihara M, Handa M, Ikebuchi K, Ikeda H (May 2001). "CrkL is an adapter for Wiskott-Aldrich syndrome protein and Syk". Blood (United States) 97 (9): 2633–9. doi:10.1182/blood.V97.9.2633. ISSN 0006-4971. PMID 11313252. 
  15. ^ a b c d Kyono, W T; de Jong R, Park R K, Liu Y, Heisterkamp N, Groffen J, Durden D L (November 1998). "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. (UNITED STATES) 161 (10): 5555–63. ISSN 0022-1767. PMID 9820532. 
  16. ^ Grumbach, I M; Mayer I A, Uddin S, Lekmine F, Majchrzak B, Yamauchi H, Fujita S, Druker B, Fish E N, Platanias L C (February 2001). "Engagement of the CrkL adaptor in interferon alpha signalling in BCR-ABL-expressing cells". Br. J. Haematol. (England) 112 (2): 327–36. doi:10.1046/j.1365-2141.2001.02556.x. ISSN 0007-1048. PMID 11167825. 
  17. ^ Ahmad, S; Alsayed Y M, Druker B J, Platanias L C (November 1997). "The type I interferon receptor mediates tyrosine phosphorylation of the CrkL adaptor protein". J. Biol. Chem. (UNITED STATES) 272 (48): 29991–4. doi:10.1074/jbc.272.48.29991. ISSN 0021-9258. PMID 9374471. 
  18. ^ Smit, L; van der Horst G, Borst J (April 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. (UNITED STATES) 271 (15): 8564–9. doi:10.1074/jbc.271.15.8564. ISSN 0021-9258. PMID 8621483. 
  19. ^ a b c Chin, H; Saito T, Arai A, Yamamoto K, Kamiyama R, Miyasaka N, Miura O (October 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. (UNITED STATES) 239 (2): 412–7. doi:10.1006/bbrc.1997.7480. ISSN 0006-291X. PMID 9344843. 
  20. ^ Wu, C; Lai C F, Mobley W C (August 2001). "Nerve growth factor activates persistent Rap1 signaling in endosomes". J. Neurosci. (United States) 21 (15): 5406–16. PMID 11466412. 
  21. ^ a b Sakkab, D; Lewitzky M, Posern G, Schaeper U, Sachs M, Birchmeier W, Feller S M (April 2000). "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. (UNITED STATES) 275 (15): 10772–8. doi:10.1074/jbc.275.15.10772. ISSN 0021-9258. PMID 10753869. 
  22. ^ a b Heaney, C; Kolibaba K, Bhat A, Oda T, Ohno S, Fanning S, Druker B J (January 1997). "Direct binding of CRKL to BCR-ABL is not required for BCR-ABL transformation". Blood (UNITED STATES) 89 (1): 297–306. ISSN 0006-4971. PMID 8978305. 
  23. ^ Ren, R; Ye Z S, Baltimore D (April 1994). "Abl protein-tyrosine kinase selects the Crk adapter as a substrate using SH3-binding sites". Genes Dev. (UNITED STATES) 8 (7): 783–95. doi:10.1101/gad.8.7.783. ISSN 0890-9369. PMID 7926767. 
  24. ^ Salgia, R; Pisick E, Sattler M, Li J L, Uemura N, Wong W K, Burky S A, Hirai H, Chen L B, Griffin J D (October 1996). "p130CAS forms a signaling complex with the adapter protein CRKL in hematopoietic cells transformed by the BCR/ABL oncogene". J. Biol. Chem. (UNITED STATES) 271 (41): 25198–203. doi:10.1074/jbc.271.41.25198. ISSN 0021-9258. PMID 8810278. 
  25. ^ a b Astier, A; Manié S N, Law S F, Canty T, Haghayghi N, Druker B J, Salgia R, Golemis E A, Freedman A S (December 1997). "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 (SWITZERLAND) 28 (1–2): 65–72. doi:10.3109/10428199709058332. ISSN 1042-8194. PMID 9498705. 
  26. ^ Ota, J; Kimura F, Sato K, Wakimoto N, Nakamura Y, Nagata N, Suzu S, Yamada M, Shimamura S, Motoyoshi K (November 1998). "Association of CrkL with STAT5 in hematopoietic cells stimulated by granulocyte-macrophage colony-stimulating factor or erythropoietin". Biochem. Biophys. Res. Commun. (UNITED STATES) 252 (3): 779–86. doi:10.1006/bbrc.1998.9445. ISSN 0006-291X. PMID 9837784. 
  27. ^ Nakamura, Takeshi; Komiya Misako, Sone Kiyoaki, Hirose Eiji, Gotoh Noriko, Morii Hiroshi, Ohta Yasutaka, Mori Nozomu (December 2002). "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. (United States) 22 (24): 8721–34. doi:10.1128/MCB.22.24.8721-8734.2002. ISSN 0270-7306. PMC 139861. PMID 12446789. 
  28. ^ Elly, C; Witte S, Zhang Z, Rosnet O, Lipkowitz S, Altman A, Liu Y C (February 1999). "Tyrosine phosphorylation and complex formation of Cbl-b upon T cell receptor stimulation". Oncogene (ENGLAND) 18 (5): 1147–56. doi:10.1038/sj.onc.1202411. ISSN 0950-9232. PMID 10022120. 
  29. ^ a b Arai, A; Kanda E, Nosaka Y, Miyasaka N, Miura O (August 2001). "CrkL is recruited through its SH2 domain to the erythropoietin receptor and plays a role in Lyn-mediated receptor signaling". J. Biol. Chem. (United States) 276 (35): 33282–90. doi:10.1074/jbc.M102924200. ISSN 0021-9258. PMID 11443118. 
  30. ^ Bai, R Y; Jahn T, Schrem S, Munzert G, Weidner K M, Wang J Y, Duyster J (August 1998). "The SH2-containing adapter protein GRB10 interacts with BCR-ABL". Oncogene (ENGLAND) 17 (8): 941–8. doi:10.1038/sj.onc.1202024. ISSN 0950-9232. PMID 9747873. 
  31. ^ Kolibaba, K S; Bhat A, Heaney C, Oda T, Druker B J (March 1999). "CRKL binding to BCR-ABL and BCR-ABL transformation". Leuk. Lymphoma (SWITZERLAND) 33 (1–2): 119–26. doi:10.3109/10428199909093732. ISSN 1042-8194. PMID 10194128. 
  32. ^ Million, Ryan P; Harakawa Nari, Roumiantsev Sergei, Varticovski Lyuba, Van Etten Richard A (June 2004). "A direct binding site for Grb2 contributes to transformation and leukemogenesis by the Tel-Abl (ETV6-Abl) tyrosine kinase". Mol. Cell. Biol. (United States) 24 (11): 4685–95. doi:10.1128/MCB.24.11.4685-4695.2004. ISSN 0270-7306. PMC 416425. PMID 15143164. 
  33. ^ Alsayed, Y; Modi S, Uddin S, Mahmud N, Druker B J, Fish E N, Hoffman R, Platanias L C (July 2000). "All-trans-retinoic acid induces tyrosine phosphorylation of the CrkL adapter in acute promyelocytic leukemia cells". Exp. Hematol. (NETHERLANDS) 28 (7): 826–32. doi:10.1016/S0301-472X(00)00170-3. ISSN 0301-472X. PMID 10907644. 
  34. ^ Lin, H; Martelli M P, Bierer B E (January 2001). "The involvement of the proto-oncogene p120 c-Cbl and ZAP-70 in CD2-mediated T cell activation". Int. Immunol. (England) 13 (1): 13–22. doi:10.1093/intimm/13.1.13. ISSN 0953-8178. PMID 11133830. 
  35. ^ Park, R K; Kyono W T, Liu Y, Durden D L (May 1998). "CBL-GRB2 interaction in myeloid immunoreceptor tyrosine activation motif signaling". J. Immunol. (UNITED STATES) 160 (10): 5018–27. ISSN 0022-1767. PMID 9590251. 
  36. ^ Taher, Taher E I; Tjin Esther P M, Beuling Esther A, Borst Jannie, Spaargaren Marcel, Pals Steven T (October 2002). "c-Cbl is involved in Met signaling in B cells and mediates hepatocyte growth factor-induced receptor ubiquitination". J. Immunol. (United States) 169 (7): 3793–800. ISSN 0022-1767. PMID 12244174. 
  37. ^ Erdreich-Epstein, A; Liu M, Kant A M, Izadi K D, Nolta J A, Durden D L (April 1999). "Cbl functions downstream of Src kinases in Fc gamma RI signaling in primary human macrophages". J. Leukoc. Biol. (UNITED STATES) 65 (4): 523–34. ISSN 0741-5400. PMID 10204582. 
  38. ^ a b Sattler, M; Salgia R, Shrikhande G, Verma S, Uemura N, Law S F, Golemis E A, Griffin J D (May 1997). "Differential signaling after beta1 integrin ligation is mediated through binding of CRKL to p120(CBL) and p110(HEF1)". J. Biol. Chem. (UNITED STATES) 272 (22): 14320–6. doi:10.1074/jbc.272.22.14320. ISSN 0021-9258. PMID 9162067. 
  39. ^ Gesbert, F; Garbay C, Bertoglio J (February 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. (UNITED STATES) 273 (7): 3986–93. doi:10.1074/jbc.273.7.3986. ISSN 0021-9258. PMID 9461587. 
  40. ^ Nishihara, Hiroshi; Maeda Masae, Oda Atsushi, Tsuda Masumi, Sawa Hirofumi, Nagashima Kazuo, Tanaka Shinya (December 2002). "DOCK2 associates with CrkL and regulates Rac1 in human leukemia cell lines". Blood (United States) 100 (12): 3968–74. doi:10.1182/blood-2001-11-0032. ISSN 0006-4971. PMID 12393632. 
  41. ^ Manié, S N; Beck A R, Astier A, Law S F, Canty T, Hirai H, Druker B J, Avraham H, Haghayeghi N, Sattler M, Salgia R, Griffin J D, Golemis E A, Freedman A S (February 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. (UNITED STATES) 272 (7): 4230–6. doi:10.1074/jbc.272.7.4230. ISSN 0021-9258. PMID 9020138. 
  42. ^ Salgia, R; Uemura N, Okuda K, Li J L, Pisick E, Sattler M, de Jong R, Druker B, Heisterkamp N, Chen L B (December 1995). "CRKL links p210BCR/ABL with paxillin in chronic myelogenous leukemia cells". J. Biol. Chem. (UNITED STATES) 270 (49): 29145–50. doi:10.1074/jbc.270.49.29145. ISSN 0021-9258. PMID 7493940. 
  43. ^ Nishiya, N; Tachibana K, Shibanuma M, Mashimo J I, Nose K (August 2001). "Hic-5-reduced cell spreading on fibronectin: competitive effects between paxillin and Hic-5 through interaction with focal adhesion kinase". Mol. Cell. Biol. (United States) 21 (16): 5332–45. doi:10.1128/MCB.21.16.5332-5345.2001. ISSN 0270-7306. PMC 87257. PMID 11463817. 

Further reading[edit]

  • Feller SM, Posern G, Voss 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, 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, et al. (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, 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, 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, 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, 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, et al. (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, 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, 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, et al. (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, 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, et al. (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.