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

Citation
Mf. Brizzi et al., Integrin-mediated adhesion of endothelial cells induces JAK2 and STAT5A activation: Role in the control of c-fos gene expression, MOL BIOL CE, 10(10), 1999, pp. 3463-3471
Citations number
43
Categorie Soggetti
Cell & Developmental Biology
Journal title
MOLECULAR BIOLOGY OF THE CELL
ISSN journal
10591524 → ACNP
Volume
10
Issue
10
Year of publication
1999
Pages
3463 - 3471
Database
ISI
SICI code
1059-1524(199910)10:10<3463:IAOECI>2.0.ZU;2-P
Abstract
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.