Structural highlights
Function
[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
PINCH is an adaptor protein found in focal adhesions, large cellular complexes that link extracellular matrix to the actin cytoskeleton. PINCH, which contains an array of five LIM domains, has been implicated as a platform for multiple protein-protein interactions that mediate integrin signaling within focal adhesions. We had previously characterized the LIM1 domain of PINCH, which functions in focal adhesions by binding specifically to integrin-linked kinase. Using NMR spectroscopy, we show here that the PINCH LIM4 domain, while maintaining the conserved LIM scaffold, recognizes the third SH3 domain of another adaptor protein, Nck2 (also called Nckbeta or Grb4), in a manner distinct from that of the LIM1 domain. Point mutation of LIM residues in the SH3-binding interface disrupted LIM-SH3 interaction and substantially impaired localization of PINCH to focal adhesions. These data provide novel structural insight into LIM domain-mediated protein-protein recognition and demonstrate that the PINCH-Nck2 interaction is an important component of the focal adhesion assembly during integrin signaling.
Structural and functional insights into PINCH LIM4 domain-mediated integrin signaling.,Velyvis A, Vaynberg J, Yang Y, Vinogradova O, Zhang Y, Wu C, Qin J Nat Struct Biol. 2003 Jul;10(7):558-64. PMID:12794636[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Velyvis A, Vaynberg J, Yang Y, Vinogradova O, Zhang Y, Wu C, Qin J. Structural and functional insights into PINCH LIM4 domain-mediated integrin signaling. Nat Struct Biol. 2003 Jul;10(7):558-64. PMID:12794636 doi:10.1038/nsb938
