The pleckstrin homology domain of Bruton tyrosine kinase interacts with protein kinase C.
Bruton tyrosine kinase (EC 2.7.1.112) [Btk, encoded by Btk in mice and BTK in humans (formerly known as atk, BPK, or emb)], which is variously mutated in chromosome X-linked agammaglobulinemia patients and X-linked immunodeficient (xid) mice, has the pleckstrin homology (PH) domain at its amino terminus. The PH domain of Btk expressed as a bacterial fusion protein directly interacts with protein kinase C in mast cell lysates. Evidence was obtained that Btk is physically associated with protein kinase C in intact murine mast cells as well. Both Ca(2+)-dependent (alpha, beta I, and beta II) and Ca(2+)-independent protein kinase C isoforms (epsilon and zeta) in mast cells interact with the PH domain of Btk in vitro, and protein kinase C beta I is associated with Btk in vivo. Btk served as a substrate of protein kinase C, and its enzymatic activity was down-regulated by protein kinase C-mediated phosphorylation. Furthermore, depletion or inhibition of protein kinase C with pharmacological agents resulted in an enhancement of the tyrosine phosphorylation of Btk induced by mast cell activation.
Yao
L
L
Division of Immunobiology, La Jolla Institute for Allergy and Immunology, CA 92037.
Kawakami
Y
Y
Kawakami
T
T
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D019000:Phosphotyrosine; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D017455:Receptors, IgE / Q000378:metabolism; D015398:Signal Transduction; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D017455:Receptors, IgE; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; C000625951:Btk protein, mouse; D011493:Protein Kinase C