Structural highlights
Function
ILK_HUMAN Receptor-proximal protein kinase regulating integrin-mediated signal transduction. May act as a mediator of inside-out integrin signaling. Focal adhesion protein part of the complex ILK-PINCH. This complex is considered to be one of the convergence points of integrin- and growth factor-signaling pathway. Could be implicated in mediating cell architecture, adhesion to integrin substrates and anchorage-dependent growth in epithelial cells. Phosphorylates beta-1 and beta-3 integrin subunit on serine and threonine residues, but also AKT1 and GSK3B.
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
Formation of a heterotrimeric IPP complex composed of integrin-linked kinase (ILK), the LIM domain protein PINCH, and parvin is important for signaling through integrin adhesion receptors. Mammals possess two PINCH genes that are expressed simultaneously in many tissues. PINCH1 and PINCH2 have overlapping functions and can compensate for one another in many settings; however, isoform-specific functions have been reported and it is proposed that association with a PINCH1- or PINCH2-containing IPP complex may provide a bifurcation point in integrin signaling promoting different cellular responses. Here we report that the LIM1 domains of PINCH1 and PINCH2 directly compete for the same binding site on the ankyrin repeat domain (ARD) of ILK. We determined the 1.9A crystal structure of the PINCH2 LIM1 domain complexed with the ARD of ILK, and show that disruption of this interface by point mutagenesis reduces binding in vitro and alters localization of PINCH2 in cells. These studies provide further evidence for the role of the PINCH LIM1 domain in association with ILK and highlight direct competition as one mechanism for regulating which PINCH isoform predominates in IPP complexes. Differential regulation of PINCH1 and PINCH2 expression may therefore provide a means for altering cellular integrin signaling pathways.
Structural basis of competition between PINCH1 and PINCH2 for binding to the ankyrin repeat domain of integrin-linked kinase.,Chiswell BP, Stiegler AL, Razinia Z, Nalibotski E, Boggon TJ, Calderwood DA J Struct Biol. 2010 Apr;170(1):157-63. Epub 2009 Dec 4. PMID:19963065[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Chiswell BP, Stiegler AL, Razinia Z, Nalibotski E, Boggon TJ, Calderwood DA. Structural basis of competition between PINCH1 and PINCH2 for binding to the ankyrin repeat domain of integrin-linked kinase. J Struct Biol. 2010 Apr;170(1):157-63. Epub 2009 Dec 4. PMID:19963065 doi:10.1016/j.jsb.2009.12.002
