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(Circulation Research. 2001;0:hh1201.092994.)
© 2001 American Heart Association, Inc.

Article

Protein Kinase C –Src Modules Direct Signal Transduction in Nitric Oxide–Induced Cardioprotection

Complex Formation as a Means for Cardioprotective Signaling

Thomas M. Vondriska¹, Jun Zhang¹, Changxu Song¹, Xian-Liang Tang, Xinan Cao, Christopher P. Baines, Jason M. Pass, Shaoshan Wang, Roberto Bolli Peipei Ping

From the Department of Physiology and Biophysics (T.M.V., J.Z., C.S., X.C., C.P.B., J.M.P., R.B., P.P.) and Division of Cardiology (T.M.V., J.Z., C.S., X.-L.T., X.C., C.P.B., J.M.P., S.W., R.B., P.P.), Department of Medicine, University of Louisville, Louisville, Ky.

Correspondence to Peipei Ping, PhD, Departments of Physiology and Biophysics, Medicine, Division of Cardiology, Suite 122 Baxter Bldg, 570 S Preston St, Louisville, KY 40202. E-mail peipeiping{at}hotmail.com

Abstract

Abstract—An essential role for protein kinase C (PKC) has been shown in multiple forms of cardioprotection; however, there is a distinct paucity of information concerning the signaling architecture that is responsible for the manifestation of a protective phenotype. We and others have recently shown that signal transduction may proceed via the formation of signaling complexes (Circ Res. 2001;88:59–62). In order to understand if the assembly of multiprotein complexes is the manner by which signaling is conducted in cardioprotection, we designed a series of experiments to characterize the associations of Src tyrosine kinase with PKC in a conscious rabbit model of nitric oxide (NO)-induced late preconditioning. Our data demonstrate that PKC and Src can form functional signaling modules in vitro: PKC interacts with Src; the association with PKC activates Src; and adult cardiac cells receiving recombinant adenoviruses encoding PKC exhibit increased Src activity. Furthermore, our results show that NO-induced late preconditioning involved PKC-Src module formation and enhanced the enzymatic activity of PKC-associated Src. Inhibition of PKC blocked cardioprotection, module formation, and PKC-associated Src activity, providing direct evidence for a functional role of the PKC-Src module in the orchestration of NO-induced cardioprotection in conscious rabbits.

Key Words: proteomics • ischemic injury • preconditioning • protein-protein interactions

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