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 extracellul ar signal-regulated kinase (ERK) pathways and result in a mitogenic respons e such as the proliferation of vascular smooth muscle cells (VSMCs). We inv estigated mechanisms of collaboration or synergism between integrins and an giotensin II involving ERK pathways in VSMCs. Integrin activation by cell a dhesion to fibronectin increased the phosphorylation level of focal adhesio n kinase (FAK) upstream of the ERK pathway. angiotensin II induced a high i ncrease in the phosphorylation level of FAK with integrin activation, but n ot in suspended cells. Integrin activation increased phosphorylation levels of ERK kinase (MEK) and ERK phosphorylation as well. Angiotensin II-induce d MEK and ERK phosphorylation were retained even in suspended cells. Furthe rmore, with integrin activation, angiotensin II induced a much larger incre ase in the phosphorylation levels of MEK and ERK. These results suggest tha t simultaneous stimulation of integrin and angiotensin II receptors cause s ynergistic interaction in the activation of ERK pathway, possibly via phosp horylation of FAK, which may play a critical role in angiotensin II-mediate d mitogenic response in VSMCs.