Signal Transduction in smooth muscle - Invited review: Focal adhesion and small heat shock proteins in the regulation of actin remodeling and contractility in smooth muscle

Smooth muscle cells are able to adapt rapidly to chemical and mechanical si gnals impinging on the cell surface. It has been suggested that dynamic cha nges in the actin cytoskeleton contribute to the processes of contractile a ctivation and mechanical adaptation in smooth muscle. In this review, evide nce for functionally important changes in actin polymerization during smoot h muscle contraction is summarized. The functions and regulation of protein s associated with "focal adhesion complexes" (membrane-associated dense pla ques) in differentiated smooth muscle, including integrins, focal adhesion kinase (FAK), c-Src, paxillin, and the 27-kDa small heat shock protein (HSP 27) are described. Integrins in smooth muscles are key elements of mechanot ransduction pathways that communicate with and are regulated by focal adhes ion proteins that include FAK, c-Src, and paxillin as well as proteins know n to mediate cytoskeletal remodeling. Evidence that functions of FAK and c- Src protein kinases are closely intertwined is discussed as well as evidenc e that focal adhesion proteins mediate key signal transduction events that regulate actin remodeling and contraction. HSP27 is reviewed as a potential ly significant effector protein that may regulate actin dynamics and cross- bridge function in response to activation of p21-activated kinase and the p 38 mitogen-activated protein kinase signaling pathway by signaling pathways linked to integrin proteins. These signaling pathways are only part of a l arge number of yet to be defined pathways that mediate acute adaptive respo nses of the cytoskeleton in smooth muscle to environmental stimuli.