MAP kinases and vascular smooth muscle function

The mitogen-activated protein (MAP) kinase family members are ubiquitously expressed protein kinases activated in response to a variety of extracellul ar stimuli and shown to be involved in cell growth, transformation, differe ntiation and apoptosis. MAP kinases have been implicated in both growth and apoptosis of vascular smooth muscle cells (VSMC) which suggests that they play important roles in cardiovascular diseases such as essential hypertens ion, atherosclerosis, and restenosis followed angioplasty. The MAP kinases are themselves components of specific kinase cascades characterized by acti vation by specific stimuli, families of related serine and threonine kinase s and downstream substrates that include other kinases, transcription facto rs, membrane receptors and other cell mediators. Cross-talk among the diffe rent MAP kinases results in direct modulation of signal transduction. In ad dition, increased expression and activation of MAP kinase phosphatases play s an important role in MAP kinase inactivation. Our laboratory has used ang iotensin II (Angll). a potent activator of all MAP kinases in VSMC, to stud y mechanisms by which MAP kinases are regulated by vasoactive peptides. In this review, we describe the mechanisms by which Angll activates MAP kinase s, and potential roles for MAP kinases in Angll- dependent effects on VSMC function.