The growth-related gene product beta induces sphingomyelin hydrolysis and activation of c-Jun N-terminal kinase in rat cerebellar granule neurones

The growth-related gene product beta (GRO beta) is a small chemoattractant cytokine that belongs to the CXC chemokine family, and GRO beta receptors a re expressed in the brain, including the cerebellum. We demonstrate that ra t cerebellar granule neurones express the GRO beta receptor CXCR2. We also show that, in addition to the known stimulation of a phosphoinositide-speci fic phospholipase C, GRO beta activates both neutral (N-) and acidic (A-) s phingomyelinases (SMase) and the stress-activated c-Jun N-terminal kinase I (JNK1). Although both exogenous ceramide and bacterial SMase stimulate JNH 1, GRO beta-induced JNK1 activation is an event probably in dependent of ce ramide generated by A-SMase, since it is maintained in the presence of comp ounds that block A-SMase activity. This is the first report on the activati on of the SMase pathway by chemokines.