Bmx, a member of the Tec family of nonreceptor tyrosine kinases, is a novel participant in pharmacological cardioprotection

Am J Physiol Heart Circ Physiol. 2004 Nov;287(5):H2364-6. doi: 10.1152/ajpheart.00416.2004. Epub 2004 Jun 10.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkaloids
  • Animals
  • Benzophenanthridines
  • Cardiotonic Agents / metabolism*
  • Cardiotonic Agents / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Myocardium / metabolism*
  • Nitric Oxide / metabolism
  • Nitric Oxide Donors / pharmacology
  • Phenanthridines / pharmacology
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism*
  • Protein Kinase C-epsilon
  • Proteomics
  • Rabbits
  • Signal Transduction / physiology


  • Alkaloids
  • Benzophenanthridines
  • Cardiotonic Agents
  • Enzyme Inhibitors
  • Intracellular Signaling Peptides and Proteins
  • Nitric Oxide Donors
  • Phenanthridines
  • Nitric Oxide
  • chelerythrine
  • Protein Kinase C
  • Protein Kinase C-epsilon