RISK-1: A novel MAPK homologue in axoplasm that is activated and retrogradely transported after nerve injury

Sensory neurons (SNs) of Aplysia are widely used to study the molecular cor relates of learning, Among these is the activation of an Aplysia (ap) MAPK that phosphorylates the transcription factor apC/EBP beta, Because crushing the axons of the SNs induces changes similar to learning, we tested the hy pothesis that apMAPK is a point of convergence on the pathways for learning and injury. One event in common is long-term hyperexcitability (LTH), and LTH was induced in the SNs after intrasomatic injection of active vertebrat e extracellular signal-regulated kinase 1 (ERK1; as an apMAPK surrogate), N erve crush activated an axoplasmic kinase at the site of injury that phosph orylated apC/EBP beta, Surprisingly, this was not apMAPK, but a kinase that was recognized by antibodies to vertebrate ERKs and to doubly phosphorylat ed, activated ERKs, The activated kinase was transported to the cell body a nd nucleus and its arrival was concurrent with an injury-induced increase i n apC/EBP beta mRNA and protein. We call this retrogradely transported kina se RISK-1. RISK-1 initiated the binding of apC/EBP beta to the ERE enhancer site in vitro and an increase in ERE-binding was detected in injured neuro ns containing active RISK-1, Thus, Aplysia neurons contain two MAPK homolog ues, one of which is a late acting retrogradely transported injury signal, (C) 2001 John Wiley & Sons, Inc.