Synergistic interaction of integrin and angiotensin II in activation of extracellular signal-regulated kinase pathways in vascular smooth muscle cells.
Integrins, major adhesion receptors and angiotensin II activate extracellular signal-regulated kinase (ERK) pathways and result in a mitogenic response such as the proliferation of vascular smooth muscle cells (VSMCs). We investigated mechanisms of collaboration or synergism between integrins and angiotensin II involving ERK pathways in VSMCs. Integrin activation by cell adhesion to fibronectin increased the phosphorylation level of focal adhesion kinase (FAK) upstream of the ERK pathway. angiotensin II induced a high increase in the phosphorylation level of FAK with integrin activation, but not in suspended cells. Integrin activation increased phosphorylation levels of ERK kinase (MEK) and ERK phosphorylation as well. Angiotensin II-induced MEK and ERK phosphorylation were retained even in suspended cells. Furthermore, with integrin activation, angiotensin II induced a much larger increase in the phosphorylation levels of MEK and ERK. These results suggest that simultaneous stimulation of integrin and angiotensin II receptors cause synergistic interaction in the activation of ERK pathway, possibly via phosphorylation of FAK, which may play a critical role in angiotensin II-mediated mitogenic response in VSMCs.
Tamura
K
K
Second Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Okazaki
M
M
Tamura
M
M
Kanegae
K
K
Okuda
H
H
Abe
H
H
Nakashima
Y
Y
D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005353:Fibronectins / Q000494:pharmacology / Q000502:physiology; D016023:Integrins / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D005353:Fibronectins; D016023:Integrins; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D020928:Mitogen-Activated Protein Kinases