Structural highlights
Function
[NCK2_HUMAN] Adapter protein which associates with tyrosine-phosphorylated growth factor receptors or their cellular substrates. Maintains low levels of EIF2S1 phosphorylation by promoting its dephosphorylation by PP1. Plays a role in ELK1-dependent transcriptional activation in response to activated Ras signaling.[1] [2] [LIMS1_HUMAN] Adapter protein in a cytoplasmic complex linking beta-integrins to the actin cytoskeleton, bridges the complex to cell surface receptor tyrosine kinases and growth factor receptors. Involved in the regulation of cell survival, cell proliferation and cell differentiation.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Weak protein-protein interactions (PPIs) (K(D) > 10(-6) M) are critical determinants of many biological processes. However, in contrast to a large growing number of well-characterized, strong PPIs, the weak PPIs, especially those with K(D) > 10(-4) M, are poorly explored. Genome wide, there exist few 3D structures of weak PPIs with K(D) > 10(-4) M, and none with K(D) > 10(-3) M. Here, we report the NMR structure of an extremely weak focal adhesion complex (K(D) approximately 3 x 10(-3) M) between Nck-2 SH3 domain and PINCH-1 LIM4 domain. The structure exhibits a remarkably small and polar interface with distinct binding modes for both SH3 and LIM domains. Such an interface suggests a transient Nck-2/PINCH-1 association process that may trigger rapid focal adhesion turnover during integrin signaling. Genetic rescue experiments demonstrate that this interface is indeed involved in mediating cell shape change and migration. Together, the data provide a molecular basis for an ultraweak PPI in regulating focal adhesion dynamics during integrin signaling.
Structure of an ultraweak protein-protein complex and its crucial role in regulation of cell morphology and motility.,Vaynberg J, Fukuda T, Chen K, Vinogradova O, Velyvis A, Tu Y, Ng L, Wu C, Qin J Mol Cell. 2005 Feb 18;17(4):513-23. PMID:15721255[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Braverman LE, Quilliam LA. Identification of Grb4/Nckbeta, a src homology 2 and 3 domain-containing adapter protein having similar binding and biological properties to Nck. J Biol Chem. 1999 Feb 26;274(9):5542-9. PMID:10026169
- ↑ Latreille M, Larose L. Nck in a complex containing the catalytic subunit of protein phosphatase 1 regulates eukaryotic initiation factor 2alpha signaling and cell survival to endoplasmic reticulum stress. J Biol Chem. 2006 Sep 8;281(36):26633-44. Epub 2006 Jul 11. PMID:16835242 doi:http://dx.doi.org/M513556200
- ↑ Vaynberg J, Fukuda T, Chen K, Vinogradova O, Velyvis A, Tu Y, Ng L, Wu C, Qin J. Structure of an ultraweak protein-protein complex and its crucial role in regulation of cell morphology and motility. Mol Cell. 2005 Feb 18;17(4):513-23. PMID:15721255 doi:10.1016/j.molcel.2004.12.031
