G-ALPHA(16) MIMICS VASOCONSTRICTOR ACTION TO INDUCE SMOOTH-MUSCLE ALPHA-ACTIN IN VASCULAR SMOOTH-MUSCLE CELLS THROUGH A JUN-NH2-TERMINAL KINASE-DEPENDENT PATHWAY

Prolonged exposure of vascular smooth muscle cells (VSMC) to vasoconst rictors such as vasopressin or angiotensin II induces hypertrophy and increases expression of muscle-specific genes including smooth muscle alpha-actin (SM-alpha-actin). These vasoconstrictors signal through G- proteins, including members of the Gq family. To further investigate t he role of Gq family members, VSMC were transfected with a constitutiv ely active mutant of a G(q) family member, G alpha(16) (G alpha(16)Q21 2L). Stable expression of G alpha(16)Q212L persistently stimulated pho spholipase C, resulting in increased basal levels of inositol phosphat es. These cells were hypertrophied and expressed elevated levels of SM -alpha-actin compared with wild-type VSMC or cells transfected with a control plasmid (Neo), SM-alpha-actin promoter activity was markedly i ncreased in cells stably or transiently expressing G alpha(16)Q212L. B asal c-Jun-NH2-terminal kinase (JNK) activity was increased 3-9-fold i n cells stably expressing G alpha(16)Q212L, while basal activity of th e p42/44 mitogen-activated protein kinases (ERKs) was unaffected, Tran sient expression of a kinase inactive JNK kinase partially inhibited i nduction of SM-alpha-actin promoter activity in response to vasoconstr ictors or expression of G alpha(16)Q212L. These results indicate that expression of constitutively active G alpha(16) in VSMC mimics the eff ects of vasoconstrictors on hypertrophy and muscle-specific gene expre ssion, and activation of JNK may play a role in these responses.