Growth factor receptors, phospholipases, phospholipid kinases and actin reorganization.

Upon binding to their ligand, several growth factor receptors that contain a tyrosine kinase within their cytoplasmic domain [receptor tyrosine kinases (RTKs)] induce a substantial reorganization of the actin cytoskeleton. This change in actin superstructure is necessary to produce multiple motile responses within the target cells. RTKs catalyse the clustering of effector proteins within functional units underneath the plasma membrane. Upon reaching a critical mass, RTK-effector units send out signals through the metabolism of membrane phospholipids and other second messenger molecules that regulate the interaction of actin with its satellite regulatory molecules. Several actin binding proteins interact transiently with small clusters of membrane inositol phospholipids in vitro (4 to 5 phospholipid molecules per actin binding protein). Such transient complex formation can either down-regulate or up-regulate the interaction of regulatory proteins with actin. The phospholipids involved in the surface catalytic control of the actin cytoskeleton are metabolically very active and abundant in cells, and are therefore poised to mediate reactions linking signal transduction molecules to the reorganization of the actin cytoskeleton upon cell activation.