Gene Symbol: Crkl
Description: v-crk avian sarcoma virus CT10 oncogene homolog-like
Alias: 1110025F07Rik, AA589403, AI325100, Crkol, crk-like protein, v-crk sarcoma virus CT10 oncogene homolog-like
Species: mouse
Products:     Crkl

Top Publications

  1. Hemmeryckx B, Reichert A, Watanabe M, Kaartinen V, de Jong R, Pattengale P, et al. BCR/ABL P190 transgenic mice develop leukemia in the absence of Crkl. Oncogene. 2002;21:3225-31 pubmed
    ..Multiple independent studies have implicated Crkl, a small adapter protein, in transduction of oncogenic signals of Bcr/Abl and Crkl tyrosine-phosphorylation is used ..
  2. 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. 1997;89:297-306 pubmed
    b>CRKL has previously been shown to be a major tyrosine phosphorylated protein in neutrophils of patients with BCR-ABL+ chronic myelogenous leukemia and in cell lines expressing BCR-ABL CRKL and BCR-ABL form a complex as demonstrated by ..
  3. Park T, Curran T. Crk and Crk-like play essential overlapping roles downstream of disabled-1 in the Reelin pathway. J Neurosci. 2008;28:13551-62 pubmed publisher
    ..Crk and Crk-like (CrkL) have been proposed to interact with tyrosine phosphorylated Dab1 to mediate downstream events in the Reelin ..
  4. Matsuki T, Pramatarova A, Howell B. Reduction of Crk and CrkL expression blocks reelin-induced dendritogenesis. J Cell Sci. 2008;121:1869-75 pubmed publisher
    ..Retrovirally expressed inhibitory RNAs used to reduce Crk and CrkL expression did not block BDNF-enhanced dendritogenesis or influence axonogenesis...
  5. Hallock P, Xu C, Park T, Neubert T, Curran T, Burden S. Dok-7 regulates neuromuscular synapse formation by recruiting Crk and Crk-L. Genes Dev. 2010;24:2451-61 pubmed publisher
  6. Guris D, Fantes J, Tara D, Druker B, Imamoto A. Mice lacking the homologue of the human 22q11.2 gene CRKL phenocopy neurocristopathies of DiGeorge syndrome. Nat Genet. 2001;27:293-8 pubmed
    ..Here we report that mice homozygous for a targeted null mutation at the CrkL locus (gene symbol Crkol for mice) exhibit defects in multiple cranial and cardiac neural crest derivatives including the cranial ganglia, ..
  7. George B, Verma R, Soofi A, Garg P, Zhang J, Park T, et al. Crk1/2-dependent signaling is necessary for podocyte foot process spreading in mouse models of glomerular disease. J Clin Invest. 2012;122:674-92 pubmed publisher
    ..Together, these observations suggest that activation of a Cas-Crk1/2-dependent complex is necessary for foot process effacement observed in distinct subsets of human glomerular diseases. ..
  8. Li L, Guris D, Okura M, Imamoto A. Translocation of CrkL to focal adhesions mediates integrin-induced migration downstream of Src family kinases. Mol Cell Biol. 2003;23:2883-92 pubmed
    The adapter protein Crk-Like (CrkL) can associate with the Src substrate p130(Cas) (Cas). The biological role of CrkL downstream of Cas, however, has been largely obscure...
  9. Ballif B, Arnaud L, Arthur W, Guris D, Imamoto A, Cooper J. Activation of a Dab1/CrkL/C3G/Rap1 pathway in Reelin-stimulated neurons. Curr Biol. 2004;14:606-10 pubmed
    ..Of these, the Crk-family proteins (CrkL, CrkI, and CrkII ), bind significant quantities of Dab1 when embryonic cortical neurons are exposed to Reelin...

More Information


  1. Cheerathodi M, Ballif B. Identification of CrkL-SH3 binding proteins from embryonic murine brain: implications for Reelin signaling during brain development. J Proteome Res. 2011;10:4453-62 pubmed publisher
    The Crk and Crk-like (CrkL) adaptor proteins play important roles in numerous signaling pathways, bridging tyrosine kinase substrates to downstream signaling effectors by virtue of their phosphotyrosine-binding SH2 domains and their ..
  2. Shao Y, Elly C, Liu Y. Negative regulation of Rap1 activation by the Cbl E3 ubiquitin ligase. EMBO Rep. 2003;4:425-31 pubmed
    ..Previous studies have proposed that Cbl is also a positive regulator of CrkL-C3G signalling, which leads to Rap1 activation...
  3. Feshchenko E, Shore S, Tsygankov A. Tyrosine phosphorylation of C-Cbl facilitates adhesion and spreading while suppressing anchorage-independent growth of V-Abl-transformed NIH3T3 fibroblasts. Oncogene. 1999;18:3703-15 pubmed
    ..phosphorylation sites of c-Cbl in these phenomena indicates that both phosphatidylinositol-3' kinase and the CrkL adaptor protein may be involved in the observed effects of c-Cbl...
  4. Haller M, Mo Q, Imamoto A, Lamb D. Murine model indicates 22q11.2 signaling adaptor CRKL is a dosage-sensitive regulator of genitourinary development. Proc Natl Acad Sci U S A. 2017;114:4981-4986 pubmed publisher
    ..2 patients exhibiting GU anomalies, we have mapped the smallest relevant region to only five genes, including CRKLCRKL encodes a src-homology adaptor protein implicated in mediating tyrosine kinase signaling, and is ..
  5. Huang Y, Clarke F, Karimi M, Roy N, Williamson E, Okumura M, et al. CRK proteins selectively regulate T cell migration into inflamed tissues. J Clin Invest. 2015;125:1019-32 pubmed publisher
    ..Using conditional knockout mice, we found that T cells lacking the adaptor proteins CRK and CRK-like (CRKL) exhibit reduced integrin-dependent adhesion, chemotaxis, and diapedesis...
  6. Sattler M, Verma S, Pride Y, Salgia R, Rohrschneider L, Griffin J. SHIP1, an SH2 domain containing polyinositol-5-phosphatase, regulates migration through two critical tyrosine residues and forms a novel signaling complex with DOK1 and CRKL. J Biol Chem. 2001;276:2451-8 pubmed
    ..a novel signaling complex with BCR/ABL that includes DOK1 (p62(DOK)), phosphatidylinositol 3-kinase (PI3K), and CRKL, each of which has been previously shown to regulate migration in diverse cell types...
  7. Lin Q, Sun M, Guo C, Shi J, Chen X, Liu S. CRKL overexpression suppresses in vitro proliferation, invasion and migration of murine hepatocarcinoma Hca-P cells. Biomed Pharmacother. 2015;69:11-7 pubmed publisher
    ..In current work, as a member of CRK family, chicken tumour virus number 10 regulator of kinase-like protein (CRKL) was revealed to be associated with malignant behaviors of Hca-P, a murine HCC cell with lymph node metastatic (LNM)..
  8. De Jong R, Haataja L, Voncken J, Heisterkamp N, Groffen J. Tyrosine phosphorylation of murine Crkl. Oncogene. 1995;11:1469-74 pubmed
    The SH2/SH3 adaptor protein Crkl is abnormally phosphorylated on tyrosine by the Bcr/Abl protein in leukemic cells from patients with Philadelphia-chromosome (Ph)positive leukemia...
  9. Seo J, Suenaga A, Hatakeyama M, Taiji M, Imamoto A. Structural and functional basis of a role for CRKL in a fibroblast growth factor 8-induced feed-forward loop. Mol Cell Biol. 2009;29:3076-87 pubmed publisher
    The adapter protein CRKL is required for the normal development of multiple tissues that rely on fibroblast growth factor 8 (FGF8). The precise role of CRKL in receptor signaling has been unclear, however...
  10. Hemmeryckx B, van Wijk A, Reichert A, Kaartinen V, De Jong R, Pattengale P, et al. Crkl enhances leukemogenesis in BCR/ABL P190 transgenic mice. Cancer Res. 2001;61:1398-405 pubmed
    The adapter protein Crkl has been implicated in the abnormal signal transduction pathways activated by the Bcr/Abl oncoprotein, which causes Philadelphia-positive leukemias in humans...
  11. Amsen D, Kruisbeek A, Bos J, Reedquist K. Activation of the Ras-related GTPase Rap1 by thymocyte TCR engagement and during selection. Eur J Immunol. 2000;30:2832-41 pubmed
    ..thymocytes, and this activation correlated with tyrosine phosphorylation of Cbl and Cbl association with CrkL. TCR-dependent Rap1 activation was enhanced by co-stimulation through CD28 and could be mimicked by treatment of ..
  12. Seo J, Wood L, Agarwal A, O Hare T, Elsea C, Griswold I, et al. A specific need for CRKL in p210BCR-ABL-induced transformation of mouse hematopoietic progenitors. Cancer Res. 2010;70:7325-35 pubmed publisher
    b>CRKL (CRK-like) is an adapter protein predominantly phosphorylated in cells that express the tyrosine kinase p210(BCR-ABL), the fusion product of a (9;22) chromosomal translocation causative for chronic myeloid leukemia...
  13. Hallock P, Chin S, Blais S, Neubert T, Glass D. Sorbs1 and -2 Interact with CrkL and Are Required for Acetylcholine Receptor Cluster Formation. Mol Cell Biol. 2016;36:262-70 pubmed publisher
    Crk and CrkL are noncatalytic adaptor proteins necessary for the formation of neuromuscular synapses which function downstream of muscle-specific kinase (MuSK), a receptor tyrosine kinase expressed in skeletal muscle, and the MuSK binding ..
  14. Miller K, Tan T, Welfare M, White S, Stark Z, Savarirayan R, et al. A mouse splice-site mutant and individuals with atypical chromosome 22q11.2 deletions demonstrate the crucial role for crkl in craniofacial and pharyngeal development. Mol Syndromol. 2014;5:276-86 pubmed publisher
    ..The CRKL gene resides within the common 3-Mb region, most frequently affected in 22q11DS, and has been shown to play an ..
  15. Panigrahi S, Stetefeld J, Jangamreddy J, Mandal S, Mandal S, Los M. Modeling of molecular interaction between apoptin, BCR-Abl and CrkL--an alternative approach to conventional rational drug design. PLoS ONE. 2012;7:e28395 pubmed publisher
    ..Adapter molecules such as Grb2 and CrkL interact with proline-rich region and activate multiple Bcr-Abl downstream signaling pathways that contribute to ..
  16. Gutierrez Berzal J, Castellano E, Martín Encabo S, Gutiérrez Cianca N, Hernandez J, Santos E, et al. Characterization of p87C3G, a novel, truncated C3G isoform that is overexpressed in chronic myeloid leukemia and interacts with Bcr-Abl. Exp Cell Res. 2006;312:938-48 pubmed
    ..p87C3G co-immunoprecipitates with both CrkL and Bcr-Abl in CML cell lines and co-immunoprecipitation between p87C3G and Bcr-Abl was also detected in primary ..
  17. Huang Z, Chen J, Regan J, Maguire C, Tang R, Dong X, et al. Loss of microRNAs in neural crest leads to cardiovascular syndromes resembling human congenital heart defects. Arterioscler Thromb Vasc Biol. 2010;30:2575-86 pubmed publisher
    ..Our results uncovered a central role for Dicer and miRNAs in NCC survival, migration, and patterning in craniofacial and cardiovascular development which, when mutated, lead to congenital neuro-craniofacial-cardiac defects. ..
  18. Moon A, Guris D, Seo J, Li L, Hammond J, Talbot A, et al. Crkl deficiency disrupts Fgf8 signaling in a mouse model of 22q11 deletion syndromes. Dev Cell. 2006;10:71-80 pubmed
    ..21 disrupt pharyngeal and cardiac development and cause DiGeorge and related human syndromes. CRKL (CRK-Like) lies within 22q11.21, and Crkl-/- mice have phenotypic features of 22q11 deletion (del22q11) syndromes...
  19. Zhang W, Shao Y, Fang D, Huang J, Jeon M, Liu Y. Negative regulation of T cell antigen receptor-mediated Crk-L-C3G signaling and cell adhesion by Cbl-b. J Biol Chem. 2003;278:23978-83 pubmed
    ..Thus, Cbl-b plays a negative role in Crk-L-C3G-mediated Rap1 and LFA-1 activation in T cells. ..
  20. 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. 2001;276:33282-90 pubmed
    ..We previously demonstrated that, in Epo-stimulated cells, an adapter protein, CrkL, becomes tyrosine-phosphorylated, physically associates with Shc, SHP-2, and Cbl, and plays a role in activation of ..
  21. Oda T, Kujovich J, Reis M, Newman B, Druker B. Identification and characterization of two novel SH2 domain-containing proteins from a yeast two hybrid screen with the ABL tyrosine kinase. Oncogene. 1997;15:1255-62 pubmed
    ..Shd was tyrosine phosphorylated in COS-7 cells co-transfected with Shd and c-Abl or Bcr-Abl. These results suggest that Shd may be a physiological substrate of c-Abl and may function as an adapter protein in the central nervous system. ..
  22. Shi J, Meng L, Sun M, Guo C, Sun X, Lin Q, et al. CRKL knockdown promotes in vitro proliferation, migration and invasion, in vivo tumor malignancy and lymph node metastasis of murine hepatocarcinoma Hca-P cells. Biomed Pharmacother. 2015;71:84-90 pubmed publisher
    Our previous study (Biomed Pharmacother 2015;69:11) demonstrated that the over-expression of CRKL, a chicken tumor virus number 10 regulator of kinase-like protein, suppresses in vitro proliferation, invasion and migration of murine ..
  23. Johnson K, Griswold I, O Hare T, Corbin A, Loriaux M, Deininger M, et al. A BCR-ABL mutant lacking direct binding sites for the GRB2, CBL and CRKL adapter proteins fails to induce leukemia in mice. PLoS ONE. 2009;4:e7439 pubmed publisher
    ..Proteins known to be associated with BCR-ABL in this complex include: GRB2, c-CBL, p62(DOK), and CRKL. These proteins in turn, link BCR-ABL to various signaling pathways indicated in cellular transformation...
  24. Yip Y, Kronstadt O Brien P, Capriotti C, Cooper J, Yip J. Migration of sympathetic preganglionic neurons in the spinal cord is regulated by Reelin-dependent Dab1 tyrosine phosphorylation and CrkL. J Comp Neurol. 2007;502:635-43 pubmed
    ..Biochemical studies show that after phosphorylation Dab1 binds to an adaptor protein, CrkL. Whether CrkL is important for Reelin signaling in vivo is unknown, because crkl(-/-) embryos die before cortical ..
  25. Guris D, Duester G, Papaioannou V, Imamoto A. Dose-dependent interaction of Tbx1 and Crkl and locally aberrant RA signaling in a model of del22q11 syndrome. Dev Cell. 2006;10:81-92 pubmed
    ..Here, we report that compound heterozygosity of mouse homologs of two 22q11 genes, CRKL and TBX1, results in a striking increase in the penetrance and expressivity of a DGS-like phenotype compared to ..
  26. Padmanabhan R, Nirmala L, Murali M, Laloraya M. CrkL is a co-activator of estrogen receptor alpha that enhances tumorigenic potential in cancer. Mol Endocrinol. 2011;25:1499-512 pubmed publisher
    ..10 regulator of kinase like (CrkL) with ER?, which was further validated by mammalian two-hybrid assay as well as coimmunoprecipitation and ..
  27. López Rivera E, Liu Y, Verbitsky M, Anderson B, Capone V, Otto E, et al. Genetic Drivers of Kidney Defects in the DiGeorge Syndrome. N Engl J Med. 2017;376:742-754 pubmed publisher
    ..In zebrafish embryos, an induced loss of function in snap29, aifm3, and crkl resulted in renal defects; the loss of crkl alone was sufficient to induce defects...
  28. George B, Fan Q, Dlugos C, Soofi A, Zhang J, Verma R, et al. Crk1/2 and CrkL form a hetero-oligomer and functionally complement each other during podocyte morphogenesis. Kidney Int. 2014;85:1382-1394 pubmed publisher
    ..As Crk1/2-null mice developed and aged normally, we tested whether the Crk1/2 paralog, CrkL, functionally complements Crk1/2 in a podocyte-specific context...
  29. Aiello F, Guszczynski T, Li W, Hixon J, Jiang Q, Hodge D, et al. IL-7-induced phosphorylation of the adaptor Crk-like and other targets. Cell Signal. 2018;47:131-141 pubmed publisher
    ..pathways related to survival, proliferation and gene expression, respectively, and increased the phosphorylation of CrkL, a member of a family of adaptors including the highly homologous Crk isoforms CrkII and CrkI, important in ..
  30. Park T, Koptyra M, Curran T. Fibroblast Growth Requires CT10 Regulator of Kinase (Crk) and Crk-like (CrkL). J Biol Chem. 2016;291:26273-26290 pubmed
    CT10 regulator of kinase (Crk) and Crk-like (CrkL) are the cellular counterparts of the viral oncogene v-Crk Elevated levels of Crk and CrkL have been observed in many human cancers; inhibition of Crk and CrkL expression reduced the tumor-..
  31. Racedo S, McDonald McGinn D, Chung J, Goldmuntz E, Zackai E, Emanuel B, et al. Mouse and human CRKL is dosage sensitive for cardiac outflow tract formation. Am J Hum Genet. 2015;96:235-44 pubmed publisher
    ..In the absence of TBX1, we hypothesized that CRKL (Crk-like), mapping to the LCR22C-D region, might contribute to the cardiac phenotype in these individuals...
  32. Park T, Curran T. Essential roles of Crk and CrkL in fibroblast structure and motility. Oncogene. 2014;33:5121-32 pubmed publisher
    Cytosolic proteins containing SH2 and SH3 domains, such as Crk and Crk-like (CrkL), are broadly expressed adapters that interact with a variety of proteins to fulfill key roles in signal transduction pathways triggered by activation of ..
  33. Voss A, Vanyai H, Collin C, Dixon M, McLennan T, Sheikh B, et al. MOZ regulates the Tbx1 locus, and Moz mutation partially phenocopies DiGeorge syndrome. Dev Cell. 2012;23:652-63 pubmed publisher
    ..Our data reveal a molecular mechanism for a specific chromatin modification of the Tbx1 locus intersecting with an environmental determinant, modeling variability in DiGeorge syndrome. ..
  34. Yanagi H, Wang L, Nishihara H, Kimura T, Tanino M, Yanagi T, et al. CRKL plays a pivotal role in tumorigenesis of head and neck squamous cell carcinoma through the regulation of cell adhesion. Biochem Biophys Res Commun. 2012;418:104-9 pubmed publisher
    ..CRK-like (CRKL) is a hematopoietic cell-dominant homologue of CRK that is reported to be phosphorylated by BCR-ABL tyrosine kinase ..
  35. Satoh T, Torii S, Nakayama K, Nishida E. CrkL is a novel target of Sprouty2 in fibroblast growth factor signaling. Genes Cells. 2010;15:161-8 pubmed publisher
    ..We find that Sprouty1 and Sprouty2 bind to the adaptor protein CrkL in a stimulus-dependent manner...
  36. Vallejo Illarramendi A, Zang K, Reichardt L. Focal adhesion kinase is required for neural crest cell morphogenesis during mouse cardiovascular development. J Clin Invest. 2009;119:2218-30 pubmed publisher
    ..Additionally, absence of Fak resulted in reduced in vivo phosphorylation of Crkl and Erk1/2, components of a signaling pathway essential for NCC development...
  37. Huang Y, Comiskey E, Dupree R, Li S, Koleske A, Burkhardt J. The c-Abl tyrosine kinase regulates actin remodeling at the immune synapse. Blood. 2008;112:111-9 pubmed publisher
    ..In addition, c-Abl is required for normal localization of WAVE2 to the immune synapse (IS). These studies identify c-Abl as a key player in the signaling cascade, leading to actin reorganization during T-cell activation. ..
  38. Schmitt J, Stork P. PKA phosphorylation of Src mediates cAMP's inhibition of cell growth via Rap1. Mol Cell. 2002;9:85-94 pubmed
    ..This study identifies an antiproliferative role for Src in the physiological regulation of cell growth by cAMP. ..
  39. Koptyra M, Park T, Curran T. Crk and CrkL are required for cell transformation by v-fos and v-ras. Mol Carcinog. 2016;55:97-104 pubmed publisher
    Crk and CrkL are SH2- and SH3-containing cytosolic adaptor proteins that can induce anchorage-independent growth of fibroblasts. Crk and CrkL play key roles in maintaining cytoskeletal integrity, cell motility and migration...
  40. Peterson A, Marks R, Fields P, Imamoto A, Gajewski T. T cell development and function in CrkL-deficient mice. Eur J Immunol. 2003;33:2687-95 pubmed
    The adapter protein CrkL has been implicated in multiple signal transduction pathways in hematopoietic cells...
  41. Uemura N, Salgia R, Li J, Pisick E, Sattler M, Griffin J. The BCR/ABL oncogene alters interaction of the adapter proteins CRKL and CRK with cellular proteins. Leukemia. 1997;11:376-85 pubmed
    ..In primary leukemic neutrophils from patients with CML, the major tyrosine phosphorylated protein is CRKL, an SH2-SH3-SH3 adapter protein which has an overall homology of 60% to CRK, the human homologue of the v-crk ..