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 regulation of gene transcription, control of cell cycle entry and survival from apoptosis. Here we investigate the involvement of the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway in integrin-mediated signaling. Plating primary human endothelial cells from umbilical cord and the human endothelial cell line ECV304 on matrix proteins or on antibody to beta1- or alphav-integrin subunits induces transient tyrosine phosphorylation of JAK2 and STAT5A. Consistent with a role for the JAK/STAT pathway in regulation of gene transcription, adhesion to matrix proteins leads to the formation of STAT5A-containing complexes with the serum-inducible element of c-fos promoter. Stable expression of a dominant negative form of STAT5A in NIH3T3 cells reduces fibronectin-induced c-fos mRNA expression, indicating the involvement of STAT5A in integrin-mediated c-fos transcription. Thus these data present a new integrin-dependent signaling mechanism involving the JAK/STAT pathway in response to cell-matrix interaction.
Brizzi
M F
MF
Department of Internal Medicine, Biology, and Biochemistry, University of Torino, 10126 Torino, Italy.
Defilippi
P
P
Rosso
A
A
Venturino
M
M
Garbarino
G
G
Miyajima
A
A
Silengo
L
L
Tarone
G
G
Pegoraro
L
L
D016475:3T3 Cells; D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D004789:Enzyme Activation / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000235:genetics*; D016762:Genes, fos; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D053614:Janus Kinase 2; D051379:Mice; D008894:Milk Proteins; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000032:analysis; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000378:metabolism; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D014162:Transfection; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D016326:Extracellular Matrix Proteins; D016023:Integrins; D008894:Milk Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D050799:STAT5 Transcription Factor; C494092:STAT5A protein, human; C494093:Stat5a protein, mouse; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2