Suboptimal cross-linking of antigen receptor induces Syk-dependent activation of p70S6 kinase through protein kinase C and phosphoinositol 3-kinase.
Ligation of the B cell antigen receptor (BCR) induces a cascade of signaling pathways that lead to clonal expansion, differentiation, or abortive activation-induced apoptosis of B lymphocytes. BCR-mediated cross-linking induces the rapid phosphorylation of protein tyrosine kinases. However, the pathways leading to the activation of downstream serine/threonine kinases such as mitogen-activated protein kinase, p90(Rsk), and p70S6 kinase (p70(S6k)) that mediate reorganization of the actin cytoskeleton, cell cycle progression, gene transcription, and protein synthesis have not been delineated. We recently demonstrated that cross-linking of BCR leads to activation of p70(S6k) in B lymphocytes. In this report, we demonstrate that multiple protein tyrosine kinase-dependent signal transduction pathways induced by BCR lead to the activation of p70(S6k). These distinct pathways exhibit different thresholds with respect to the extent of receptor cross-linking required for their activation. Activation of p70(S6k) by suboptimal doses of anti-Ig is Syk-dependent and is mediated by protein kinase C and phosphoinositol 3-kinase. Moreover, the activation of p70(S6k) results in phosphorylation of S6 protein which is important for ribosomal protein synthesis and may be coupled to BCR-induced protein and DNA synthesis in primary murine B cells.
Li
H L
HL
Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
Davis
W
W
Puré
E
E
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D002384:Catalysis / Q000187:drug effects; D002478:Cells, Cultured; D002645:Chickens; D004261:DNA Replication / Q000187:drug effects; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism*; D005434:Flow Cytometry; D047908:Intracellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism*; D020123:Sirolimus / Q000494:pharmacology; D013154:Spleen / Q000166:cytology; D000072377:Syk Kinase
D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D011947:Receptors, Antigen, B-Cell; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; D019893:Ribosomal Protein S6 Kinases; D011493:Protein Kinase C; D020123:Sirolimus