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Gene Review

NCK1  -  NCK adaptor protein 1

Homo sapiens

Synonyms: Cytoplasmic protein NCK1, NCK, NCKalpha, Nck-1, SH2/SH3 adaptor protein NCK-alpha, ...
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Disease relevance of NCK1


High impact information on NCK1

  • Two papers, one in Nature (Jones et al., 2006) and the other in the Journal of Clinical Investigation (Verma et al., 2006) show that Nck adaptor proteins connect phosphorylated nephrin with actin polymerization in podocyte foot processes, structures important for slit-diaphragm formation in the kidney [4].
  • In contrast, a mutant Dok (DokY361F), in which Tyr361 was replaced by phenylalanine, failed to bind NCK but partially retained the ability to bind rasGAP in response to insulin [5].
  • Two of these proteins represented the tyrosine kinase fyn and the mouse homologue of phospholipase C-gamma 1, whereas two genes encoded proteins similar to v-crk and NCK [6].
  • We also found that NCK binds directly to the guanine nucleotide exchange factor SOS [7].
  • We found that in NIH 3T3 cells, NCK strongly activates this promoter [7].

Biological context of NCK1

  • CONCLUSION: These results demonstrate that localization of Pak1 to the membrane in the absence of other signals is sufficient for its activation, and imply that the Nck adaptor protein could function to link changes in tyrosine phosphorylation of cellular proteins to the Cdc42/Pak signaling pathway [8].
  • To identify potential downstream effectors of NCK we screened a bacterial expression library to isolate proteins that bind its SH3 domains [9].
  • Although the association of NCK with activated receptor protein-tyrosine kinases, via its SH2 domain, implicates NCK as a mediator of growth factor-induced signal transduction, little is known about the pathway(s) downstream of NCK recruitment [9].

Anatomical context of NCK1


Associations of NCK1 with chemical compounds


Physical interactions of NCK1

  • SOCS7 interacts with septins and NCK through distinct domains [16].

Other interactions of NCK1


  1. Localization of human ARF2 and NCK genes and 13 other NotI-linking clones to chromosome 3 by fluorescence in situ hybridization. Vorobieva, N., Protopopov, A., Protopopova, M., Kashuba, V., Allikmets, R.L., Modi, W., Zabarovsky, E.R., Klein, G., Kisselev, L., Graphodatsky, A. Cytogenet. Cell Genet. (1995) [Pubmed]
  2. EspFU is a translocated EHEC effector that interacts with Tir and N-WASP and promotes Nck-independent actin assembly. Campellone, K.G., Robbins, D., Leong, J.M. Dev. Cell (2004) [Pubmed]
  3. Protective effect of transferrin C3 in lung cancer? Beckman, L.E., Van Landeghem, G.F., Sikström, C., Lundgren, R., Beckman, L. Oncology (1999) [Pubmed]
  4. Nck links nephrin to actin in kidney podocytes. Tryggvason, K., Pikkarainen, T., Patrakka, J. Cell (2006) [Pubmed]
  5. Tyrosine phosphorylation of p62(Dok) induced by cell adhesion and insulin: possible role in cell migration. Noguchi, T., Matozaki, T., Inagaki, K., Tsuda, M., Fukunaga, K., Kitamura, Y., Kitamura, T., Shii, K., Yamanashi, Y., Kasuga, M. EMBO J. (1999) [Pubmed]
  6. High-efficiency expression/cloning of epidermal growth factor-receptor-binding proteins with Src homology 2 domains. Margolis, B., Silvennoinen, O., Comoglio, F., Roonprapunt, C., Skolnik, E., Ullrich, A., Schlessinger, J. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  7. Binding of NCK to SOS and activation of ras-dependent gene expression. Hu, Q., Milfay, D., Williams, L.T. Mol. Cell. Biol. (1995) [Pubmed]
  8. Activation of Pak by membrane localization mediated by an SH3 domain from the adaptor protein Nck. Lu, W., Katz, S., Gupta, R., Mayer, B.J. Curr. Biol. (1997) [Pubmed]
  9. Isolation of a NCK-associated kinase, PRK2, an SH3-binding protein and potential effector of Rho protein signaling. Quilliam, L.A., Lambert, Q.T., Mickelson-Young, L.A., Westwick, J.K., Sparks, A.B., Kay, B.K., Jenkins, N.A., Gilbert, D.J., Copeland, N.G., Der, C.J. J. Biol. Chem. (1996) [Pubmed]
  10. NCK and PAK participate in the signaling pathway by which vascular endothelial growth factor stimulates the assembly of focal adhesions. Stoletov, K.V., Ratcliffe, K.E., Spring, S.C., Terman, B.I. J. Biol. Chem. (2001) [Pubmed]
  11. A novel ligand for SH3 domains. The Nck adaptor protein binds to a serine/threonine kinase via an SH3 domain. Chou, M.M., Hanafusa, H. J. Biol. Chem. (1995) [Pubmed]
  12. Association of Nck with tyrosine-phosphorylated SLP-76 in activated T lymphocytes. Wunderlich, L., Faragó, A., Downward, J., Buday, L. Eur. J. Immunol. (1999) [Pubmed]
  13. Nck adaptor proteins link nephrin to the actin cytoskeleton of kidney podocytes. Jones, N., Blasutig, I.M., Eremina, V., Ruston, J.M., Bladt, F., Li, H., Huang, H., Larose, L., Li, S.S., Takano, T., Quaggin, S.E., Pawson, T. Nature (2006) [Pubmed]
  14. The phosphotyrosine peptide binding specificity of Nck1 and Nck2 Src homology 2 domains. Frese, S., Schubert, W.D., Findeis, A.C., Marquardt, T., Roske, Y.S., Stradal, T.E., Heinz, D.W. J. Biol. Chem. (2006) [Pubmed]
  15. A dominant-negative p65 PAK peptide inhibits angiogenesis. Kiosses, W.B., Hood, J., Yang, S., Gerritsen, M.E., Cheresh, D.A., Alderson, N., Schwartz, M.A. Circ. Res. (2002) [Pubmed]
  16. Septins regulate actin organization and cell-cycle arrest through nuclear accumulation of NCK mediated by SOCS7. Kremer, B.E., Adang, L.A., Macara, I.G. Cell (2007) [Pubmed]
  17. Chromosome locations of genes encoding human signal transduction adapter proteins, Nck (NCK), Shc (SHC1), and Grb2 (GRB2). Huebner, K., Kastury, K., Druck, T., Salcini, A.E., Lanfrancone, L., Pelicci, G., Lowenstein, E., Li, W., Park, S.H., Cannizzaro, L. Genomics (1994) [Pubmed]
  18. Enhanced phosphatidylinositol 3-kinase activity and high phosphorylation state of its downstream signalling molecules mediated by ret with the MEN 2B mutation. Murakami, H., Iwashita, T., Asai, N., Shimono, Y., Iwata, Y., Kawai, K., Takahashi, M. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  19. Novel Src homology 3 domain-binding motifs identified from proteomic screen of a Pro-rich region. Jia, C.Y., Nie, J., Wu, C., Li, C., Li, S.S. Mol. Cell Proteomics (2005) [Pubmed]
  20. Inducible clustering of membrane-targeted SH3 domains of the adaptor protein Nck triggers localized actin polymerization. Rivera, G.M., Briceño, C.A., Takeshima, F., Snapper, S.B., Mayer, B.J. Curr. Biol. (2004) [Pubmed]
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