SELECTIVE NEURAL CELL-ADHESION MOLECULE SIGNALING BY SRC FAMILY TYROSINE KINASES AND TYROSINE PHOSPHATASES

Nerve growth cone guidance is a highly complex feat, involving coordin ation of cell adhesion molecules, trophic factor gradients, and extrac ellular matrix proteins'. While navigating through the developing nerv ous system, the growth cone must integrate diverse environmental signa ls into a singular response. The repertoire of growth cone responses t o these extracellular cues includes axonal growth, fasciculation, and synaptic stabilization, which are achieved through dynamic changes in the cytoskeleton and modulation of gene expression. It has become evid ent that interactions between cell adhesion molecules can activate int racellular signaling pathways in neurons(2-4). Such signaling pathways are just beginning to be defined for the axonal growth promoting mole cules L1 and NCAM which are members of the immunoglobulin (Ig) superfa mily. Recent findings have revealed that L1 and NCAM induce neurite ou tgrowth by activating intracellular signaling pathways in the growth c one mediated by two different members of the si-e family of nonrecepto r protein tyrosine kinases (PTKs), pp60(c-src) and p59(fyn5,6). Growth cones display diverse morphologies and variable motility on these dif ferent cell adhesion molecules(7-10), which are likely to be generated by src kinases. In this review we will address novel features of nonr eceptor PTKs of the si-e family which dictate their distinctive molecu lar interactions with cell adhesion molecules and signaling components .