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J Cell Sci. 2009 Jun 1;122(Pt 11):1800-11. doi: 10.1242/jcs.044602. Epub 2009 May 12.

Molecular dissection of the ILK-PINCH-parvin triad reveals a fundamental role for the ILK kinase domain in the late stages of focal-adhesion maturation.

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1
Institute of Developmental Biology and Cancer Research, University of Nice-Sophia Antiopolis, CNRS-UMR6543, Centre Antoine Lacassagne, 33 Avenue de Valombrose, 06189 Nice, France.

Abstract

Integrin-linked kinase (ILK) and cytoplasmic adaptors of the PINCH and parvin families form a ternary complex, termed IPP, that localizes to integrin adhesions. We show here that deletion of the genes encoding ILK or PINCH1 similarly blocks maturation of focal adhesions to tensin-rich and phosphotyrosine-poor fibrillar adhesions (FBs) by downregulating expression or recruitment of tensin and destabilizing alpha5beta1-integrin-cytoskeleton linkages. As IPP components are interdependent for integrin targeting and protein stability, functional dissection of the complex was achieved by fusing ILK, PINCH, parvin or their individual motifs to the cytoplasmic tail of beta3 integrin, normally excluded from FBs. Using this novel gain-of-function approach, we demonstrated that expression of the C-terminal kinase domain of ILK can restore tensin recruitment and prompt focal-adhesion maturation in IPP-null cells. Debilitating mutations in the paxillin- or ATP-binding sites of ILK, together with alpha-parvin silencing, revealed a determinant role for ILK-parvin association, but not for direct paxillin binding, in this function. We propose a model in which the C-terminal domain of ILK promotes integrin sorting by reinforcing alpha5beta1-integrin-actin linkage and controls force transmission by targeting tensin to maturing adhesions.

PMID:
19435803
DOI:
10.1242/jcs.044602
[Indexed for MEDLINE]
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