LAR protein tyrosine phosphatase regulates focal adhesions via CDK1

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Colleges, School and Institutes

Abstract

Focal adhesions are complex multi-molecular structures that link the actin cytoskeleton to the extracellular matrix via integrin adhesion receptors and play a key role in regulation of many cellular functions. LAR is a receptor protein tyrosine phosphatase that regulates PDGF signalling and localises to focal adhesions. We have observed that loss of LAR phosphatase activity in mouse embryonic fibroblasts results in reduced numbers of focal adhesions and decreased adhesion to fibronectin. To understand how LAR regulates cell adhesion we used phosphoproteomic data, comparing global phosphorylation events in wild type and LAR phosphatase-deficient cells, to analyse differential kinase activity. Kinase prediction analysis of LAR-regulated phosphosites identified a node of cytoskeleton- and adhesion-related proteins centred on cyclin-dependent kinase-1 (CDK1). We found that loss of LAR activity resulted in reduced activity of CDK1, and that CDK1 activity was required for LAR-mediated focal adhesion complex formation. We also established that LAR regulates CDK1 activity via c-Abl and PKB/Akt. In summary, we have identified a novel role for a receptor protein tyrosine phosphatase in regulating CDK1 activity and hence cell adhesion to the extracellular matrix.

Details

Original languageEnglish
Pages (from-to)2962-2971
JournalJournal of Cell Science
Volume129
Early online date27 Jun 2016
Publication statusPublished - 1 Aug 2016

Keywords

  • CDK1, focal adhesions, PTPRF, LAR phosphatase, cell adhesion

ASJC Scopus subject areas