Adhesion molecule L1 stimulates neuronal migration through Vav2-Pak1 signaling.

Organized neuronal migration and guided axon outgrowth are key determinants of the development of the functional nervous system. L1, a member of the Ig superfamily of cell surface receptors, stimulates cell migration and neurite outgrowth through the MAP kinases ERK1, 2. The signaling molecules participating in this signaling cascade have only partly been identified. Here it is shown that L1 clustering activates the guanine nucleotide exchange factor (GEF) Vav2 and the Rac1 effector p21 associated kinase 1 (Pak1). Also, we found that Pak1 kinase activity contributes to ERK activation by L1, and is necessary for L1-potentiated haptotactic cell migration. A signaling pathway is proposed from L1 through Vav2, Rac1, Pak1 and ERK that may be important for L1 mediated neuronal cell migration.