Nerve growth factor induces activation of MAP-kinase and p90rsk in human B lymphocytes.
A previous report from this laboratory demonstrated that human B lymphocytes expressed nerve growth factor (NGF) receptors on their surface. On the basis of NGF enhancement of B cell proliferation these receptors 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-lymphoblastoid cell lines with NGF induced the tyrosine phosphorylation and activation of the p42erk-2 isoform of MAP-kinase (MAPK). In addition, NGF induced shifts in the mobility of p90 ribosomal S6 kinase (p90rsk) on immunoblots and increased p90rsk kinase activity in immunoprecipitates. NGF-induced shifts in p90rsk mobility displayed similar dose and time kinetics as NGF-induced MAPK activation. Activation of both MAPK and p90rsk occurred with doses of NGF as low as 400 pg/ml. Preincubation of NGF with anti-NGF Ab inhibited NGF-induced activation of MAPK and p90rsk. These results demonstrate that the interaction of NGF with its receptor on human B cells results in the stimulation of major components of the signaling pathway also initiated by NGF-receptor ligation in cells of neuronal origin.
Franklin
R A
RA
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206, USA.
Brodie
C
C
Melamed
I
I
Terada
N
N
Lucas
J J
JJ
Gelfand
E W
EW
D001402:B-Lymphocytes / Q000201:enzymology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation; D006801:Humans; D015151:Immunoblotting; D009414:Nerve Growth Factors / Q000276:immunology / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D019893:Ribosomal Protein S6 Kinases; D015398:Signal Transduction / Q000502:physiology
D009414:Nerve Growth Factors; D017346:Protein Serine-Threonine Kinases; D019893:Ribosomal Protein S6 Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases