LAR protein tyrosine phosphatase regulates focal adhesions through CDK1.
J Cell Sci
; 129(15): 2962-71, 2016 08 01.
Article
en En
| MEDLINE
| ID: mdl-27352860
ABSTRACT
Focal adhesions are complex multi-molecular structures that link the actin cytoskeleton to the extracellular matrix through integrin adhesion receptors and play a key role in regulation of many cellular functions. LAR (also known as PTPRF) 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 through c-Abl and Akt family proteins. In summary, we have identified a new role for a receptor protein tyrosine phosphatase in regulating CDK1 activity and hence cell adhesion to the extracellular matrix.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteína Quinasa CDC2
/
Adhesiones Focales
/
Proteínas Tirosina Fosfatasas Clase 2 Similares a Receptores
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Cell Sci
Año:
2016
Tipo del documento:
Article
País de afiliación:
Reino Unido