Differential activation of ERKs to focal adhesions by PKC epsilon is required for PMA-induced adhesion and migration of human glioma cells

Protein kinase C (PKC) is. a family of serine/threonine kinases. involved i n. the transduction of a variety of signals. There is increasing evidence t o indicate that specific PKC isoforms are involved in the regulation of dis tinct cellular processes. In glioma, cells, PKC alpha was found to be a cri tical regulator of proliferation and cell cycle progression, white PKC epsi lon was found to regulate adhesion and migration. Herein, we. report that s pecific PKC isoforms are able to differentially activate extracellular-sign al regulated kinase (ERK)! in distinct cellular locations: while PKC alpha induces the activation of nuclear ERK, PKC epsilon induces, the activation of ERK at focal adhesions. Inhibition of the ERK pathway completely abolish ed the PKC-induced integrin-mediated adhesion and migration. Thus, we prese nt the first evidence that PKC epsilon is able to, activate ERK at focal ad hesions to mediate glioma cell adhesion and motility, providing a molecular mechanism to. explain the different biological functions of PKC alpha and epsilon in glioma cells.