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J Cell Sci. 2018 Oct 26;131(20). pii: jcs221184. doi: 10.1242/jcs.221184.

Kindlin-2 interacts with a highly conserved surface of ILK to regulate focal adhesion localization and cell spreading.

Author information

1
From the Department of Pharmacology, Yale University, New Haven CT 06510, USA.
2
From the Department of Pharmacology, Yale University, New Haven CT 06510, USA david.calderwood@yale.edu.
3
Department of Cell Biology, Yale University, New Haven CT 06510, USA.

Abstract

The integrin-associated adaptor proteins integrin-linked kinase (ILK) and kindlin-2 play central roles in integrin signaling and control of cell morphology. A direct ILK-kindlin-2 interaction is conserved across species and involves the F2PH subdomain of kindlin-2 and the pseudokinase domain (pKD) of ILK. However, complete understanding of the ILK-kindlin-2 interaction and its role in integrin-mediated signaling has been impeded by difficulties identifying the binding site for kindlin-2 on ILK. We used conservation-guided mapping to dissect the interaction between ILK and kindlin-2 and identified a previously unknown binding site for kindlin-2 on the C-lobe of the pKD of ILK. Mutations at this site inhibit binding to kindlin-2 while maintaining structural integrity of the pKD. Importantly, kindlin-binding-defective ILK mutants exhibit impaired focal adhesion localization and fail to fully rescue the spreading defects seen in ILK knockdown cells. Furthermore, kindlin-2 mutants with impaired ILK binding are also unable to fully support cell spreading. Thus, the interaction between ILK and kindlin-2 is critical for cell spreading and focal adhesion localization, representing a key signaling axis downstream of integrins.This article has an associated First Person interview with the first author of the paper.

KEYWORDS:

Integrin; Integrin-linked kinase; Kindlin-2

PMID:
30254023
PMCID:
PMC6215391
[Available on 2019-10-15]
DOI:
10.1242/jcs.221184
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