CRKL

Crk-like protein is a protein that in humans is encoded by the CRKL gene.[5][6]

CRKL
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesCRKL, CRK like proto-oncogene, adaptor protein
External IDsOMIM: 602007 MGI: 104686 HomoloGene: 38021 GeneCards: CRKL
Gene location (Human)
Chr.Chromosome 22 (human)[1]
Band22q11.21Start20,917,407 bp[1]
End20,953,747 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

1399

12929

Ensembl

ENSG00000099942

ENSMUSG00000006134

UniProt

P46109

P47941

RefSeq (mRNA)

NM_005207

NM_001277231
NM_007764

RefSeq (protein)

NP_005198

NP_001264160
NP_031790

Location (UCSC)Chr 22: 20.92 – 20.95 MbChr 16: 17.45 – 17.49 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

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.[7]

CrkL together with Crk participates in the Reelin signaling cascade downstream of DAB1.[8][9]

Interactions

CRKL has been shown to interact with:


See also

References
  1. GRCh38: Ensembl release 89: ENSG00000099942 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000006134 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 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.
  6. Senechal K, Halpern J, Sawyers CL (September 1996). "The CRKL adaptor protein transforms fibroblasts and functions in transformation by the BCR-ABL oncogene". The Journal of Biological Chemistry. 271 (38): 23255–61. doi:10.1074/jbc.271.38.23255. PMID 8798523.
  7. "Entrez Gene: CRKL v-crk sarcoma virus CT10 oncogene homolog (avian)-like".
  8. Matsuki T, Pramatarova A, Howell BW (June 2008). "Reduction of Crk and CrkL expression blocks reelin-induced dendritogenesis". Journal of Cell Science. 121 (11): 1869–75. doi:10.1242/jcs.027334. PMC 2430739. PMID 18477607.
  9. Park TJ, Curran T (December 2008). "Crk and Crk-like play essential overlapping roles downstream of disabled-1 in the Reelin pathway". The Journal of Neuroscience. 28 (50): 13551–62. doi:10.1523/JNEUROSCI.4323-08.2008. PMC 2628718. PMID 19074029.
  10. Kyono WT, de Jong R, Park RK, Liu Y, Heisterkamp N, Groffen J, Durden DL (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)". Journal of Immunology. 161 (10): 5555–63. PMID 9820532.
  11. Heaney C, Kolibaba K, Bhat A, Oda T, Ohno S, Fanning S, Druker BJ (January 1997). "Direct binding of CRKL to BCR-ABL is not required for BCR-ABL transformation". Blood. 89 (1): 297–306. doi:10.1182/blood.V89.1.297. PMID 8978305.
  12. Ren R, Ye ZS, Baltimore D (April 1994). "Abl protein-tyrosine kinase selects the Crk adapter as a substrate using SH3-binding sites". Genes & Development. 8 (7): 783–95. doi:10.1101/gad.8.7.783. PMID 7926767.
  13. Salgia R, Pisick E, Sattler M, Li JL, Uemura N, Wong WK, Burky SA, Hirai H, Chen LB, Griffin JD (October 1996). "p130CAS forms a signaling complex with the adapter protein CRKL in hematopoietic cells transformed by the BCR/ABL oncogene". The Journal of Biological Chemistry. 271 (41): 25198–203. doi:10.1074/jbc.271.41.25198. PMID 8810278.
  14. Astier A, Manié SN, Law SF, Canty T, Haghayghi N, Druker BJ, Salgia R, Golemis EA, Freedman AS (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". Leukemia & Lymphoma. 28 (1–2): 65–72. doi:10.3109/10428199709058332. PMID 9498705.
  15. Bai RY, Jahn T, Schrem S, Munzert G, Weidner KM, Wang JY, Duyster J (August 1998). "The SH2-containing adapter protein GRB10 interacts with BCR-ABL". Oncogene. 17 (8): 941–8. doi:10.1038/sj.onc.1202024. PMID 9747873.
  16. Kolibaba KS, Bhat A, Heaney C, Oda T, Druker BJ (March 1999). "CRKL binding to BCR-ABL and BCR-ABL transformation". Leukemia & Lymphoma. 33 (1–2): 119–26. doi:10.3109/10428199909093732. PMID 10194128.
  17. Million RP, Harakawa N, Roumiantsev S, Varticovski L, Van Etten RA (June 2004). "A direct binding site for Grb2 contributes to transformation and leukemogenesis by the Tel-Abl (ETV6-Abl) tyrosine kinase". Molecular and Cellular Biology. 24 (11): 4685–95. doi:10.1128/MCB.24.11.4685-4695.2004. PMC 416425. PMID 15143164.
  18. Elly C, Witte S, Zhang Z, Rosnet O, Lipkowitz S, Altman A, Liu YC (February 1999). "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.
  19. van Dijk TB, van Den Akker E, Amelsvoort MP, 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. 96 (10): 3406–13. doi:10.1182/blood.V96.10.3406. PMID 11071635.
  20. Sattler M, Salgia R, Shrikhande G, Verma S, Pisick E, Prasad KV, Griffin JD (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)". The Journal of Biological Chemistry. 272 (15): 10248–53. doi:10.1074/jbc.272.15.10248. PMID 9092574.
  21. Felschow DM, McVeigh ML, Hoehn GT, Civin CI, Fackler MJ (June 2001). "The adapter protein CrkL associates with CD34". Blood. 97 (12): 3768–75. doi:10.1182/blood.v97.12.3768. PMID 11389015.
  22. 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". Biochemical and Biophysical Research Communications. 239 (2): 412–7. doi:10.1006/bbrc.1997.7480. PMID 9344843.
  23. Alsayed Y, Modi S, Uddin S, Mahmud N, Druker BJ, Fish EN, Hoffman R, Platanias LC (July 2000). "All-trans-retinoic acid induces tyrosine phosphorylation of the CrkL adapter in acute promyelocytic leukemia cells". Experimental Hematology. 28 (7): 826–32. doi:10.1016/s0301-472x(00)00170-3. PMID 10907644.
  24. Lin H, Martelli MP, Bierer BE (January 2001). "The involvement of the proto-oncogene p120 c-Cbl and ZAP-70 in CD2-mediated T cell activation". International Immunology. 13 (1): 13–22. doi:10.1093/intimm/13.1.13. PMID 11133830.
  25. Park RK, Kyono WT, Liu Y, Durden DL (May 1998). "CBL-GRB2 interaction in myeloid immunoreceptor tyrosine activation motif signaling". Journal of Immunology. 160 (10): 5018–27. PMID 9590251.
  26. Taher TE, Tjin EP, Beuling EA, Borst J, Spaargaren M, Pals ST (October 2002). "c-Cbl is involved in Met signaling in B cells and mediates hepatocyte growth factor-induced receptor ubiquitination". Journal of Immunology. 169 (7): 3793–800. doi:10.4049/jimmunol.169.7.3793. PMID 12244174.
  27. Erdreich-Epstein A, Liu M, Kant AM, Izadi KD, Nolta JA, Durden DL (April 1999). "Cbl functions downstream of Src kinases in Fc gamma RI signaling in primary human macrophages". Journal of Leukocyte Biology. 65 (4): 523–34. doi:10.1002/jlb.65.4.523. PMID 10204582.
  28. Sattler M, Salgia R, Shrikhande G, Verma S, Uemura N, Law SF, Golemis EA, Griffin JD (May 1997). "Differential signaling after beta1 integrin ligation is mediated through binding of CRKL to p120(CBL) and p110(HEF1)". The Journal of Biological Chemistry. 272 (22): 14320–6. doi:10.1074/jbc.272.22.14320. PMID 9162067.
  29. 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". The Journal of Biological Chemistry. 273 (7): 3986–93. doi:10.1074/jbc.273.7.3986. PMID 9461587.
  30. Nishihara H, Maeda M, Oda A, Tsuda M, Sawa H, Nagashima K, Tanaka S (December 2002). "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.
  31. 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". The Journal of Biological Chemistry. 276 (35): 33282–90. doi:10.1074/jbc.M102924200. PMID 11443118.
  32. Sakkab D, Lewitzky M, Posern G, Schaeper U, Sachs M, Birchmeier W, Feller SM (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". The Journal of Biological Chemistry. 275 (15): 10772–8. doi:10.1074/jbc.275.15.10772. PMID 10753869.
  33. 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 Letters. 495 (3): 148–53. doi:10.1016/s0014-5793(01)02373-0. PMID 11334882.
  34. Oehrl W, Kardinal C, Ruf S, Adermann K, Groffen J, Feng GS, Blenis J, Tan TH, Feller SM (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. 17 (15): 1893–901. doi:10.1038/sj.onc.1202108. PMID 9788432.
  35. Ling P, Yao Z, Meyer CF, Wang XS, Oehrl W, Feller SM, Tan TH (February 1999). "Interaction of hematopoietic progenitor kinase 1 with adapter proteins Crk and CrkL leads to synergistic activation of c-Jun N-terminal kinase". Molecular and Cellular Biology. 19 (2): 1359–68. doi:10.1128/MCB.19.2.1359. PMC 116064. PMID 9891069.
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  37. Shi CS, Tuscano J, Kehrl JH (February 2000). "Adaptor proteins CRK and CRKL associate with the serine/threonine protein kinase GCKR promoting GCKR and SAPK activation". Blood. 95 (3): 776–82. doi:10.1182/blood.V95.3.776.003k23_776_782. PMID 10648385.
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  39. Salgia R, Uemura N, Okuda K, Li JL, Pisick E, Sattler M, de Jong R, Druker B, Heisterkamp N, Chen LB (December 1995). "CRKL links p210BCR/ABL with paxillin in chronic myelogenous leukemia cells". The Journal of Biological Chemistry. 270 (49): 29145–50. doi:10.1074/jbc.270.49.29145. PMID 7493940.
  40. Nishiya N, Tachibana K, Shibanuma M, Mashimo JI, Nose K (August 2001). "Hic-5-reduced cell spreading on fibronectin: competitive effects between paxillin and Hic-5 through interaction with focal adhesion kinase". Molecular and Cellular Biology. 21 (16): 5332–45. doi:10.1128/MCB.21.16.5332-5345.2001. PMC 87257. PMID 11463817.
  41. Grumbach IM, Mayer IA, Uddin S, Lekmine F, Majchrzak B, Yamauchi H, Fujita S, Druker B, Fish EN, Platanias LC (February 2001). "Engagement of the CrkL adaptor in interferon alpha signalling in BCR-ABL-expressing cells". British Journal of Haematology. 112 (2): 327–36. doi:10.1046/j.1365-2141.2001.02556.x. PMID 11167825.
  42. Ahmad S, Alsayed YM, Druker BJ, Platanias LC (November 1997). "The type I interferon receptor mediates tyrosine phosphorylation of the CrkL adaptor protein". The Journal of Biological Chemistry. 272 (48): 29991–4. doi:10.1074/jbc.272.48.29991. PMID 9374471.
  43. 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". The Journal of Biological Chemistry. 271 (15): 8564–9. doi:10.1074/jbc.271.15.8564. PMID 8621483.
  44. Wu C, Lai CF, Mobley WC (August 2001). "Nerve growth factor activates persistent Rap1 signaling in endosomes". The Journal of Neuroscience. 21 (15): 5406–16. doi:10.1523/JNEUROSCI.21-15-05406.2001. PMID 11466412.
  45. Nakamura T, Komiya M, Sone K, Hirose E, Gotoh N, Morii H, Ohta Y, Mori N (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". Molecular and Cellular Biology. 22 (24): 8721–34. doi:10.1128/mcb.22.24.8721-8734.2002. PMC 139861. PMID 12446789.
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  47. Oda A, Ochs HD, Lasky LA, 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. 97 (9): 2633–9. doi:10.1182/blood.v97.9.2633. PMID 11313252.

Further reading
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