Intracellular signaling by the neural cell adhesion molecule.

Cell adhesion molecules are known to play far more complex roles than mechanically attaching one cell to an adjacent cell or to components of the extracellular matrix. Thus, important roles for cell adhesion molecules in the regulation of intracellular signaling pathways have been revealed. In this review, we discuss the present knowledge about signaling pathways activated upon homophilic binding of the neural cell adhesion molecule (NCAM). Homophilic NCAM binding leads to activation of a signal transduction pathway involving Ca2+ through activation of the fibroblast growth factor receptor, and to activation of the mitogen-activated protein kinase pathway. In addition, cyclic adenosine monophosphate and protein kinase A are involved in NCAM-mediated signaling. Among these pathways the possibility exists of cross talk or convergence, of which different possible mediators have been suggested. Finally, several downstream effector molecules leading to NCAM-mediated cellular endpoints have been demonstrated, including transcription factors and regulators of the cytoskeleton.