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Biochem J ; 378(Pt 2): 559-67, 2004 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-14629195

RESUMO

Focal adhesion kinase (FAK) is an intracellular kinase that localizes to focal adhesions. FAK is overexpressed in human tumours, and FAK regulates both cellular adhesion and anti-apoptotic survival signalling. Disruption of FAK function by overexpression of the FAK C-terminal domain [FAK-CD, analogous to the FRNK (FAK-related non-kinase) protein] leads to loss of adhesion and apoptosis in tumour cells. We have shown that overexpression of an activated form of the Src tyrosine kinase suppressed the loss of adhesion induced by dominant-negative; adenoviral FAK-CD and decreased the apoptotic response in BT474 and MCF-7 breast cancer cell lines. This adhesion-dependent apoptosis was increased by the Src-family kinase inhibitor PP2 [4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine]. We have also shown that expression of activated Src in breast cancer cells increased the expression of alpha2-integrin and that overexpression of alpha2-integrin suppressed FAK-CD-mediated loss of adhesion. Our results suggest a model in which Src regulates adhesion and survival through enhanced expression of the alpha2-integrin. This provides a mechanism through which Src promotes cellular adhesion and alters the adhesive function of FAK.


Assuntos
Neoplasias da Mama/metabolismo , Integrina alfa2/metabolismo , Proteínas Proto-Oncogênicas pp60(c-src)/metabolismo , Apoptose , Neoplasias da Mama/enzimologia , Neoplasias da Mama/patologia , Adesão Celular , Linhagem Celular Tumoral , Sobrevivência Celular , Proteínas do Citoesqueleto/metabolismo , Ativação Enzimática , Feminino , Quinase 1 de Adesão Focal , Proteína-Tirosina Quinases de Adesão Focal , Humanos , Paxilina , Fosfoproteínas/metabolismo , Estrutura Terciária de Proteína , Proteínas Tirosina Quinases/química , Proteínas Tirosina Quinases/metabolismo
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