TYROSINE KINASE PATHWAYS AND THE REGULATION OF SMOOTH-MUSCLE CONTRACTILITY

Epidermal growth factor (EGF) mediates three tyrosine kinase-dependent smooth muscle response paradigms, two of which comprise a rapid increase in muscle tension and one of which is characterized by an agonist-mediated reduction in sensitivity to other agents. The three types of response are mediated via distinct signal transduction pathways, and marked tissue and species variation have been observed, even for a single growth factor agonist. Vasoactive agents, such as angiotensin II and vasopressin, that act via G protein-coupled receptors can also work via tyrosine kinase pathways to cause contraction in some of the same intact smooth muscle preparations that contract in response to EGF. In this review, Morley Hollenberg discusses the tyrosine kinase-modulated signal transduction pathways for EGF and also agonists that act via G protein-coupled receptors, and hypothesizes that there may be an intermediary non-receptor tyrosine kinase that may serve as a point of convergence for the contractile actions of these agents in smooth muscle.