NERVE GROWTH-FACTOR INDUCES ACTIVATION OF MAP-KINASE AND P90(RSK) IN HUMAN B-LYMPHOCYTES

A previous report from this laboratory demonstrated that human B lymph ocytes expressed nerve growth factor (NCF) receptors on their surface. On the basis of NCF enhancement of B cell proliferation these recepto rs are presumed to be functional. We have now characterized one of the signaling pathways that NGF may utilize in the functional activation of B lymphocytes. Stimulation of three different human B-lymphoblastoi d cell lines with NGF induced the tyrosine phosphorylation and activat ion of the p42(erk-2) isoform of MAP-kinase (MAPK). In addition, NGF i nduced shifts in the mobility of p90 ribosomal S6 kinase (p90(rsk)) on immunoblots and increased p90(rsk) kinase activity in immunoprecipita tes. NGF-induced shifts in p90(rsk) mobility displayed similar dose an d time kinetics as NG F-induced MAPK activation. Activation of both MA PK and p90(rsk) occurred with doses of NCF as low as 400 pg/ml. Preinc ubation of NGF with anti-NGF Ab inhibited NGF-induced activation of MA PK and p90(rsk). These results demonstrate that the interaction of NGF with its receptor on human B cells results in the stimulation of majo r components of the signaling pathway also initiated by NGF-receptor l igation in cells of neuronal origin.