Integrin-mediated adhesion of endothelial cells induces JAK2 and STAT5A activation: Role in the control of c-fos gene expression

Integrin-mediated adhesion induces several signaling pathways leading to re gulation of gene transcription, control of cell cycle entry and survival fr om apoptosis. Here we investigate the involvement of the Janus kinase (JAK) /signal transducers and activators of transcription (STAT) pathway in integ rin-mediated signaling. Plating primary human endothelial cells from umbili cal cord and the human endothelial cell:line ECV304 on matrix proteins or o n antibody to beta 1- or alpha v-integrin subunits induces transient tyrosi ne phosphorylation of JAK2 and STAT5A. Consistent with a role for the JAK/S TAT pathway in regulation of gene transcription, adhesion to matrix protein s leads to the formation of STAT5A-containing complexes with the serum-indu cible element of c-fos promoter. Stable expression of a dominant negative f orm of STAT5A in NIH3T3 cells reduces fibronectin-induced c-fos mRNA expres sion, indicating the involvement of STAT5A in integrin-mediated c-fos trans cription. Thus these data present a new integrin-dependent signaling mechan ism involving the JAK/STAT pathway in response to cell-matrix interaction.