Activation and phosphatidylinositol 3-kinase-dependent phosphorylation of protein kinase C-epsilon by the B cell antigen receptor.
Protein kinase C (PKC) enzymes play an important role in B cell antigen receptor (BCR) signaling, linking the BCR to the activation of mitogen-activated protein kinases as well as the NF-kappa B, and AP-1 transcription factors. There are eleven different PKC isoforms, each of which is likely to have a unique set of substrates and hence a unique role in signal transduction. Although PKC-alpha, PKC-beta, PKC-delta, and PKC-zeta have been shown to be targets of BCR signaling, the full spectrum of PKC enzymes that are activated by the BCR remains to be determined. In this report, we show that PKC-epsilon is a target of BCR signaling. We found that PKC-epsilon is highly expressed in B cells and that BCR engagement causes PKC-epsilon to translocate from the cytosol to cellular membranes. This presumably reflects the binding of PKC-epsilon to its membrane-associated lipid activator, diacylglycerol. We also found that BCR engagement resulted in the phosphatidylinositol 3-kinase-dependent phosphorylation of PKC-epsilon. This modification may promote the full activation of PKC-epsilon. Activation of PKC-epsilon could be a key event in BCR signaling since PKC-epsilon has been strongly linked to cell survival and proliferation in other cell types.
Ting
Helen C
HC
Department of Microbiology and Immunology, University of British Columbia, 6174 University Blvd., Vancouver, BC, Canada V6T 1Z3.
Christian
Sherri L
SL
Burgess
Anita E
AE
Gold
Michael R
MR
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D002462:Cell Membrane / Q000502:physiology; D007527:Isoenzymes / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D051744:Protein Kinase C-epsilon; D021381:Protein Transport / Q000502:physiology; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*
D007527:Isoenzymes; D011947:Receptors, Antigen, B-Cell; D019869:Phosphatidylinositol 3-Kinases; C497256:Prkce protein, mouse; D011493:Protein Kinase C; D051744:Protein Kinase C-epsilon