LAR protein tyrosine phosphatase regulates focal adhesions via CDK1

Research output: Contribution to journalArticlepeer-review

Standard

LAR protein tyrosine phosphatase regulates focal adhesions via CDK1. / Almuntafeky, Adil Rashid Sarhan; Patel, Trushar; Cowell, Alana; Tomlinson, Michael; Hellberg, Karina; Heath, John; Cunningham, Debbie; Hotchin, Neil.

In: Journal of Cell Science, Vol. 129, 01.08.2016, p. 2962-2971.

Research output: Contribution to journalArticlepeer-review

Harvard

APA

Vancouver

Author

Bibtex

@article{5c548337ec5a4f8b9744b2361ca593f1,
title = "LAR protein tyrosine phosphatase regulates focal adhesions via CDK1",
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.",
keywords = "CDK1, focal adhesions, PTPRF, LAR phosphatase, cell adhesion",
author = "Almuntafeky, {Adil Rashid Sarhan} and Trushar Patel and Alana Cowell and Michael Tomlinson and Karina Hellberg and John Heath and Debbie Cunningham and Neil Hotchin",
year = "2016",
month = aug,
day = "1",
doi = "10.1242/jcs.191379",
language = "English",
volume = "129",
pages = "2962--2971",
journal = "J. Cell Sci",
issn = "0021-9533",
publisher = "The Company of Biologists Ltd.",

}

RIS

TY - JOUR

T1 - LAR protein tyrosine phosphatase regulates focal adhesions via CDK1

AU - Almuntafeky, Adil Rashid Sarhan

AU - Patel, Trushar

AU - Cowell, Alana

AU - Tomlinson, Michael

AU - Hellberg, Karina

AU - Heath, John

AU - Cunningham, Debbie

AU - Hotchin, Neil

PY - 2016/8/1

Y1 - 2016/8/1

N2 - 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.

AB - 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.

KW - CDK1

KW - focal adhesions

KW - PTPRF

KW - LAR phosphatase

KW - cell adhesion

U2 - 10.1242/jcs.191379

DO - 10.1242/jcs.191379

M3 - Article

VL - 129

SP - 2962

EP - 2971

JO - J. Cell Sci

JF - J. Cell Sci

SN - 0021-9533

ER -