NCK2

{{Short description|Protein-coding gene in the species Homo sapiens}}

{{Infobox_gene}}

Cytoplasmic protein NCK2 (also known as NCK-beta and Grb4) is a protein that in humans is encoded by the NCK2 gene.{{cite journal | vauthors = Liu J, Li M, Ran X, Fan JS, Song J | title = Structural insight into the binding diversity between the human Nck2 SH3 domains and proline-rich proteins | journal = Biochemistry | volume = 45 | issue = 23 | pages = 7171–84 | date = Jun 2006 | pmid = 16752908 | doi = 10.1021/bi060091y }}{{cite web | title = Entrez Gene: NCK2 NCK adaptor protein 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8440}}

Function

NCK belongs to family of adaptor proteins. There are two mammalian NCK genes, NCK1 and NCK2. NCK1 is located in chromosome 3 and NCK2 is located in chromosome 2. The protein contains three SH3 domains and one SH2 domain. The protein has no known catalytic function but has been shown to bind and recruit various proteins involved in the regulation of receptor protein tyrosine kinases. It is through these regulatory activities that this protein is believed to be involved in cytoskeletal reorganization. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.

Interactions

NCK2 has been shown to interact with:

{{div col|colwidth=20em}}

  • Epidermal growth factor receptor,{{cite journal | vauthors = Chen M, She H, Davis EM, Spicer CM, Kim L, Ren R, Le Beau MM, Li W | title = Identification of Nck family genes, chromosomal localization, expression, and signaling specificity | journal = The Journal of Biological Chemistry | volume = 273 | issue = 39 | pages = 25171–8 | date = Sep 1998 | pmid = 9737977 | doi = 10.1074/jbc.273.39.25171| doi-access = free }}{{cite journal | vauthors = Braverman LE, Quilliam LA | title = Identification of Grb4/Nckbeta, a src homology 2 and 3 domain-containing adapter protein having similar binding and biological properties to Nck | journal = The Journal of Biological Chemistry | volume = 274 | issue = 9 | pages = 5542–9 | date = Feb 1999 | pmid = 10026169 | doi = 10.1074/jbc.274.9.5542| doi-access = free }}
  • LIMS1,{{cite journal | vauthors = Tu Y, Li F, Goicoechea S, Wu C | title = The LIM-only protein PINCH directly interacts with integrin-linked kinase and is recruited to integrin-rich sites in spreading cells | journal = Molecular and Cellular Biology | volume = 19 | issue = 3 | pages = 2425–34 | date = Mar 1999 | pmid = 10022929 | pmc = 84035 | doi = 10.1128/mcb.19.3.2425}}{{cite journal | vauthors = Tu Y, Li F, Wu C | title = Nck-2, a novel Src homology2/3-containing adaptor protein that interacts with the LIM-only protein PINCH and components of growth factor receptor kinase-signaling pathways | journal = Molecular Biology of the Cell | volume = 9 | issue = 12 | pages = 3367–82 | date = Dec 1998 | pmid = 9843575 | pmc = 25640 | doi = 10.1091/mbc.9.12.3367}}
  • PDGFRB,{{cite journal | vauthors = Chen M, She H, Kim A, Woodley DT, Li W | title = Nckbeta adapter regulates actin polymerization in NIH 3T3 fibroblasts in response to platelet-derived growth factor bb | journal = Molecular and Cellular Biology | volume = 20 | issue = 21 | pages = 7867–80 | date = Nov 2000 | pmid = 11027258 | pmc = 86398 | doi = 10.1128/mcb.20.21.7867-7880.2000}}
  • PTK2,{{cite journal | vauthors = Goicoechea SM, Tu Y, Hua Y, Chen K, Shen TL, Guan JL, Wu C | title = Nck-2 interacts with focal adhesion kinase and modulates cell motility | journal = The International Journal of Biochemistry & Cell Biology | volume = 34 | issue = 7 | pages = 791–805 | date = Jul 2002 | pmid = 11950595 | doi = 10.1016/s1357-2725(02)00002-x}}
  • T-cell surface glycoprotein CD3 epsilon chain{{cite journal | vauthors = Gil D, Schamel WW, Montoya M, Sánchez-Madrid F, Alarcón B | title = Recruitment of Nck by CD3 epsilon reveals a ligand-induced conformational change essential for T cell receptor signaling and synapse formation | journal = Cell | volume = 109 | issue = 7 | pages = 901–12 | date = Jun 2002 | pmid = 12110186 | doi = 10.1016/S0092-8674(02)00799-7| s2cid = 2714623 | doi-access = free }} and
  • TrkB.{{cite journal | vauthors = Suzuki S, Mizutani M, Suzuki K, Yamada M, Kojima M, Hatanaka H, Koizumi S | title = Brain-derived neurotrophic factor promotes interaction of the Nck2 adaptor protein with the TrkB tyrosine kinase receptor | journal = Biochemical and Biophysical Research Communications | volume = 294 | issue = 5 | pages = 1087–92 | date = Jun 2002 | pmid = 12074588 | doi = 10.1016/S0006-291X(02)00606-X }}

{{Div col end}}

References

{{reflist}}

Further reading

{{refbegin | 2}}

  • {{cite journal | vauthors = Li W, Hu P, Skolnik EY, Ullrich A, Schlessinger J | title = The SH2 and SH3 domain-containing Nck protein is oncogenic and a common target for phosphorylation by different surface receptors | journal = Molecular and Cellular Biology | volume = 12 | issue = 12 | pages = 5824–33 | date = Dec 1992 | pmid = 1333047 | pmc = 360522 | doi = 10.1128/MCB.12.12.5824 }}
  • {{cite journal | vauthors = Tu Y, Li F, Wu C | title = Nck-2, a novel Src homology2/3-containing adaptor protein that interacts with the LIM-only protein PINCH and components of growth factor receptor kinase-signaling pathways | journal = Molecular Biology of the Cell | volume = 9 | issue = 12 | pages = 3367–82 | date = Dec 1998 | pmid = 9843575 | pmc = 25640 | doi = 10.1091/mbc.9.12.3367 }}
  • {{cite journal | vauthors = Tu Y, Li F, Goicoechea S, Wu C | title = The LIM-only protein PINCH directly interacts with integrin-linked kinase and is recruited to integrin-rich sites in spreading cells | journal = Molecular and Cellular Biology | volume = 19 | issue = 3 | pages = 2425–34 | date = Mar 1999 | pmid = 10022929 | pmc = 84035 | doi = 10.1128/mcb.19.3.2425}}
  • {{cite journal | vauthors = Braverman LE, Quilliam LA | title = Identification of Grb4/Nckbeta, a src homology 2 and 3 domain-containing adapter protein having similar binding and biological properties to Nck | journal = The Journal of Biological Chemistry | volume = 274 | issue = 9 | pages = 5542–9 | date = Feb 1999 | pmid = 10026169 | doi = 10.1074/jbc.274.9.5542 | doi-access = free }}
  • {{cite journal | vauthors = Coutinho S, Jahn T, Lewitzky M, Feller S, Hutzler P, Peschel C, Duyster J | title = Characterization of Ggrb4, an adapter protein interacting with Bcr-Abl | journal = Blood | volume = 96 | issue = 2 | pages = 618–24 | date = Jul 2000 | pmid = 10887126 | doi = 10.1182/blood.V96.2.618}}
  • {{cite journal | vauthors = Chen M, She H, Kim A, Woodley DT, Li W | title = Nckbeta adapter regulates actin polymerization in NIH 3T3 fibroblasts in response to platelet-derived growth factor bb | journal = Molecular and Cellular Biology | volume = 20 | issue = 21 | pages = 7867–80 | date = Nov 2000 | pmid = 11027258 | pmc = 86398 | doi = 10.1128/MCB.20.21.7867-7880.2000 }}
  • {{cite journal | vauthors = Tu Y, Kucik DF, Wu C | title = Identification and kinetic analysis of the interaction between Nck-2 and DOCK180 | journal = FEBS Letters | volume = 491 | issue = 3 | pages = 193–9 | date = Mar 2001 | pmid = 11240126 | doi = 10.1016/S0014-5793(01)02195-0 | s2cid = 31372015 | doi-access = free }}
  • {{cite journal | vauthors = Jahn T, Seipel P, Coutinho S, Miething C, Peschel C, Duyster J | title = Grb4/Nckbeta acts as a nuclear repressor of v-Abl-induced transcription from c-jun/c-fos promoter elements | journal = The Journal of Biological Chemistry | volume = 276 | issue = 46 | pages = 43419–27 | date = Nov 2001 | pmid = 11514578 | doi = 10.1074/jbc.M107030200 | doi-access = free }}
  • {{cite journal | vauthors = Cowan CA, Henkemeyer M | title = The SH2/SH3 adaptor Grb4 transduces B-ephrin reverse signals | journal = Nature | volume = 413 | issue = 6852 | pages = 174–9 | date = Sep 2001 | pmid = 11557983 | doi = 10.1038/35093123 | bibcode = 2001Natur.413..174C | s2cid = 4313061 }}
  • {{cite journal | vauthors = Goicoechea SM, Tu Y, Hua Y, Chen K, Shen TL, Guan JL, Wu C | title = Nck-2 interacts with focal adhesion kinase and modulates cell motility | journal = The International Journal of Biochemistry & Cell Biology | volume = 34 | issue = 7 | pages = 791–805 | date = Jul 2002 | pmid = 11950595 | doi = 10.1016/S1357-2725(02)00002-X }}
  • {{cite journal | vauthors = Suzuki S, Mizutani M, Suzuki K, Yamada M, Kojima M, Hatanaka H, Koizumi S | title = Brain-derived neurotrophic factor promotes interaction of the Nck2 adaptor protein with the TrkB tyrosine kinase receptor | journal = Biochemical and Biophysical Research Communications | volume = 294 | issue = 5 | pages = 1087–92 | date = Jun 2002 | pmid = 12074588 | doi = 10.1016/S0006-291X(02)00606-X }}
  • {{cite journal | vauthors = Gil D, Schamel WW, Montoya M, Sánchez-Madrid F, Alarcón B | title = Recruitment of Nck by CD3 epsilon reveals a ligand-induced conformational change essential for T cell receptor signaling and synapse formation | journal = Cell | volume = 109 | issue = 7 | pages = 901–12 | date = Jun 2002 | pmid = 12110186 | doi = 10.1016/S0092-8674(02)00799-7 | s2cid = 2714623 | doi-access = free }}
  • {{cite journal | vauthors = Song J, Vranken W, Xu P, Gingras R, Noyce RS, Yu Z, Shen SH, Ni F | title = Solution structure and backbone dynamics of the functional cytoplasmic subdomain of human ephrin B2, a cell-surface ligand with bidirectional signaling properties | journal = Biochemistry | volume = 41 | issue = 36 | pages = 10942–9 | date = Sep 2002 | pmid = 12206665 | doi = 10.1021/bi025815u }}
  • {{cite journal | vauthors = Aspenström P | title = The WASP-binding protein WIRE has a role in the regulation of the actin filament system downstream of the platelet-derived growth factor receptor | journal = Experimental Cell Research | volume = 279 | issue = 1 | pages = 21–33 | date = Sep 2002 | pmid = 12213210 | doi = 10.1006/excr.2002.5576 }}
  • {{cite journal | vauthors = Hafizi S, Alindri F, Karlsson R, Dahlbäck B | title = Interaction of Axl receptor tyrosine kinase with C1-TEN, a novel C1 domain-containing protein with homology to tensin | journal = Biochemical and Biophysical Research Communications | volume = 299 | issue = 5 | pages = 793–800 | date = Dec 2002 | pmid = 12470648 | doi = 10.1016/S0006-291X(02)02718-3 }}
  • {{cite journal | vauthors = Velyvis A, Vaynberg J, Yang Y, Vinogradova O, Zhang Y, Wu C, Qin J | title = Structural and functional insights into PINCH LIM4 domain-mediated integrin signaling | journal = Nature Structural Biology | volume = 10 | issue = 7 | pages = 558–64 | date = Jul 2003 | pmid = 12794636 | doi = 10.1038/nsb938 | s2cid = 175531 }}
  • {{cite journal | vauthors = Hu Y, Fang X, Dunham SM, Prada C, Stachowiak EK, Stachowiak MK | title = 90-kDa ribosomal S6 kinase is a direct target for the nuclear fibroblast growth factor receptor 1 (FGFR1): role in FGFR1 signaling | journal = The Journal of Biological Chemistry | volume = 279 | issue = 28 | pages = 29325–35 | date = Jul 2004 | pmid = 15117958 | doi = 10.1074/jbc.M311144200 | doi-access = free }}
  • {{cite journal | vauthors = Ran X, Song J | title = Structural insight into the binding diversity between the Tyr-phosphorylated human ephrinBs and Nck2 SH2 domain | journal = The Journal of Biological Chemistry | volume = 280 | issue = 19 | pages = 19205–12 | date = May 2005 | pmid = 15764601 | doi = 10.1074/jbc.M500330200 | doi-access = free }}
  • {{cite journal | vauthors = Song J | title = Tyrosine phosphorylation of the well packed ephrinB cytoplasmic beta-hairpin for reverse signaling. Structural consequences and binding properties | journal = The Journal of Biological Chemistry | volume = 278 | issue = 27 | pages = 24714–20 | date = Jul 2003 | pmid = 12606549 | doi = 10.1074/jbc.M210625200 | doi-access = free }}
  • {{cite journal | vauthors = Liu Z, Guo X, Jiang Y, Zhang H | title = NCK2 is significantly associated with opiates addiction in African-origin men | journal = TheScientificWorldJournal | volume = 2013 | pages = 748979 | year = 2013 | pmid = 23533358 | doi = 10.1155/2013/748979 | pmc=3603435| doi-access = free }}

{{refend}}