Protein kinase C mu (PKC mu) associates with the B cell antigen receptor complex and regulates lymphocyte signaling.
We have identified a Ser/Thr kinase associated with the B cell receptor (BCR) complex as protein kinase C mu (PKC mu). PKC mu activity is up-regulated after cross-linking the BCR and CD19 on B cells, and PKC mu co-precipitates with Syk and phospholipase C-gamma 1/2 (PLC gamma 1/2). In vitro phosphorylation of fusion proteins showed that both Syk and PLC gamma 1 are potential substrates of PKC mu in vivo. Analysis of mutants of the chicken B cell line DT40 deficient in either Syk, Lyn, Btk, or PLC gamma 2 revealed that BCR-induced activation of PKC mu, like activation of PLC gamma 2, requires Syk and is partially regulated by Btk, but is Lyn independent. PKC mu can down-regulate the ability of Syk to phosphorylate PLC gamma 1 in vitro. Thus, PKC mu may function in a negative feedback loop regulating BCR-initiated signaling cascades.
Sidorenko
S P
SP
Department of Microbiology, University of Washington, Seattle 98195, USA.
Law
C L
CL
Klaus
S J
SJ
Chandran
K A
KA
Takata
M
M
Kurosaki
T
T
Clark
E A
EA
D001402:B-Lymphocytes / Q000502:physiology*; D004792:Enzyme Precursors / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000378:metabolism; D051966:Phospholipase C gamma; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D015398:Signal Transduction; D000072377:Syk Kinase; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism
D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D010750:Phosphoproteins; D011947:Receptors, Antigen, B-Cell; D019000:Phosphotyrosine; C089212:protein kinase D; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D011493:Protein Kinase C; D010738:Type C Phospholipases; D051966:Phospholipase C gamma