NERVE GROWTH-FACTOR SIGNAL-TRANSDUCTION IN HUMAN B-LYMPHOCYTES IS MEDIATED BY GP140(TRK)

Nerve growth factor (NGF) plays an important role in the regulation of the immune system. Recent studies from this laboratory demonstrated t he presence of functional NGF receptors on human B lymphocytes; in add ition, NGF has been shown to enhance B lymphocyte proliferation. NGF c aused both concentration- and time-dependent increases in tyrosine pho sphorylation of five proteins of 140, 110, 85, 60 and 42 kDa, which we re identified as phospholipase C-gamma 1, phosphatidylinositol-3 kinas e and mitogen-activated protein kinase. To elucidate the contribution of the Trk family of tyrosine kinases to the phosphorylation events in duced by NGF, we identified gp140(trk) in human B cells and in human B cell lines. Analysis of specific gp140(trk) immunoprecipitates indica ted that addition of NGF to B cells induced a rapid increase in the ty rosine phosphorylation of gp140(trk) and inhibition of this phosphoryl ation prevented the tyrosine phosphorylation of other proteins. These data identify the central role of gp140(trk) in NGF signaling of human B lymphocytes.