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
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.