Protein kinase C epsilon-Src modules direct signal transduction in nitric oxide-induced cardioprotection - Complex formation as a means for cardioprotective signaling
Tm. Vondriska et al., Protein kinase C epsilon-Src modules direct signal transduction in nitric oxide-induced cardioprotection - Complex formation as a means for cardioprotective signaling, CIRCUL RES, 88(12), 2001, pp. 1306-1313
An essential role for protein kinase C epsilon (PKC epsilon) has been shown
in multiple forms of cardioprotection; however, there is a distinct paucit
y of information concerning the signaling architecture that is responsible
for the manifestation of a protective phenotype, We and others have recentl
y shown that signal transduction may proceed via the formation of signaling
complexes (Circ Res, 2001;88:59-62), In order to understand if the assembl
y of multiprotein complexes is the manner by which signaling is conducted i
n cardioprotection, we designed a series of experiments to characterize the
associations of Src tyrosine kinase with PKC epsilon in a conscious rabbit
model of nitric oxide (NO)-induced late preconditioning. Our data demonstr
ate that PKC epsilon and Src can form functional signaling modules in vitro
: PKC epsilon interacts with Src; the association with PKC epsilon activate
s Src; and adult cardiac cells receiving recombinant adenoviruses encoding
PKC epsilon exhibit increased Src activity. Furthermore, our results show t
hat NO-induced late preconditioning involved PKC epsilon -Src module format
ion and enhanced the enzymatic activity of PKC epsilon -associated Src. inh
ibition of PKC blocked cardioprotection, module formation, and PKC epsilon
-associated Src activity, providing direct evidence for a functional role o
f the PKC epsilon -Src module in the orchestration of NO-induced cardioprot
ection in conscious rabbits.