PKC{epsilon} activation induces dichotomous cardiac phenotypes and modulates PKC{epsilon}-RACK interactions and RACK expression

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 280; no. 3; p. H946
• Main Authors: Pass, Jason M, Zheng, Yuting, Wead, William B, Zhang, Jun, Li, Richard C. X, Bolli, Roberto, Ping, Peipei
• Format: Journal Article
• Language: English
• Published: 01.03.2001
• ISSN: 0363-6135; 1522-1539

1  Division of Cardiology, Department of Medicine, and 2  Department of Physiology and Biophysics, University of Louisville, Louisville, Kentucky 40292 Receptors for activated C kinase (RACKs) have been shown to facilitate activation of protein kinase C (PKC). However, it is unknown whether PKC activation modulates RACK protein expression and PKC-RACK interactions. This issue was studied in two PKC transgenic lines exhibiting dichotomous cardiac phenotypes: one exhibits increased resistance to myocardial ischemia (cardioprotected phenotype) induced by a modest increase in PKC activity (228   ± 23% of control), whereas the other exhibits cardiac hypertrophy and failure (hypertrophied phenotype) induced by a marked increase in PKC activity (452 ± 28% of control). Our data demonstrate that activation of PKC modulates the expression of RACK isotypes and PKC-RACK interactions in a PKC activity- and dosage-dependent fashion. We found that, in mice displaying the cardioprotected phenotype, activation of PKC enhanced RACK2 expression (178 ±   13% of control) and particulate PKC -RACK2 protein-protein interactions (178 ± 18% of control). In contrast, in mice displaying the hypertrophied phenotype, there was not only an increase in RACK2 expression (330 ± 33% of control) and particulate PKC -RACK2 interactions (154 ± 14% of control) but also in RACK1 protein expression (174   ± 10% of control). Most notably, PKC -RACK1 interactions were identified in this line. With the use of transgenic mice expressing a dominant negative PKC , we found that the changes in RACK expression as well as the attending cardiac phenotypes were dependent on PKC activity. Our observations demonstrate that RACK expression is dynamically regulated by PKC and suggest that differential patterns of PKC -RACK interactions may be important determinants of PKC -dependent cardiac phenotypes. protein-protein interactions; cardiac phenotypes; protein kinase C; transgenic mouse; receptors for activated C kinase