Bmx, a member of the Tec family of nonreceptor tyrosine kinases, is a novel participant in pharmacological cardioprotection.
Previous studies have indicated that PKC-epsilon is a central regulator of protective signal transduction in the heart. However, the signaling modules through which PKC-epsilon exerts its protective effects have only begun to be understood. We have identified a novel participant in the PKC-epsilon signaling system in cardioprotection, the nonreceptor tyrosine kinase Bmx. Functional proteomic analyses of PKC-epsilon signaling complexes identified Bmx as a member of these complexes. Subsequent studies in rabbits have indicated that Bmx is activated by nitric oxide (NO) in the heart, concomitant with the late phase of NO donor-induced protection, and provide the first analysis of Bmx expression/distribution in the setting of cardioprotection. In addition, increased expression of Bmx induced by NO donors was blocked by the same mechanism that blocked cardioprotection: inhibition of PKC with chelerythrine. These findings indicate that a novel type of PKC-tyrosine kinase module (involving Bmx) is formed in the heart and may be involved in pharmacological cardioprotection by NO donors.
Zhang
Jun
J
Department of Physiology, Cardiovascular Research Laboratories, Suite 1619 MRL Bldg., 675 Charles E. Young Dr., David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Ping
Peipei
P
Wang
Guang-Wu
GW
Lu
Ming
M
Pantaleon
Dawn
D
Tang
Xian-Liang
XL
Bolli
Roberto
R
Vondriska
Thomas M
TM
D000470:Alkaloids; D000818:Animals; D053119:Benzophenanthridines; D002316:Cardiotonic Agents / Q000378:metabolism* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010617:Phenanthridines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051744:Protein Kinase C-epsilon; D040901:Proteomics; D011817:Rabbits; D015398:Signal Transduction / Q000502:physiology
D000470:Alkaloids; D053119:Benzophenanthridines; D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D020030:Nitric Oxide Donors; D010617:Phenanthridines; D009569:Nitric Oxide; C016299:chelerythrine; D011493:Protein Kinase C; D051744:Protein Kinase C-epsilon