© 2000 American Heart Association, Inc.
Editorials |
Protein Kinase C and Myocardial Biology and Function
From the Joslin Diabetes Center, Research Division, Harvard Medical School, Boston, Mass.
Correspondence to George L. King, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215. E-mail george.king@joslin.harvard.edu
Key Words: protein kinase C • cardiac • growth • contractility • ischemic preconditioning
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Introduction |
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Activation of protein kinase C (PKC) and its various isoforms has been postulated to have multiple cardiovascular functions, including vascular permeability, cell migration and growth, extracellular matrix production, and expression of various cytokines.1 2 The ability of PKC to regulate many cardiovascular functions is not surprising, because PKC, a family of serine-threonine kinases, is an intracellular signal for many cardiovasotropic growth factors, such as angiotensin, endothelin, and vascular endothelial growth and permeability factor.3 4 5 In addition, PKC activation can indirectly modulate other signal pathways, such as the Raf-MEK1–MAP kinase and PI3 kinase–Akt cascades.6 7
The physiological importance of PKC can also be
surmised by the existence of multiple isoforms, of which 12 members
have been documented to date. These are usually arranged according to
their structure and substrate requirements into the following groups:
conventional PKCs (cPKCs) (
, ß1/2, and 
),
which are Ca2+ dependent and activated by
binding to diacylglycerol (DAG) and
phosphatidylserine (PS); novel PKCs (nPKCs) (
,
, 
, and 
), which are Ca2+ independent
but are activated by DAG and PS; and atypical PKCs (aPKCs) (
and 
/
), which are Ca2+ and DAG independent
but are PS sensitive. The distribution of the various PKC isoforms is
tissue and species dependent. In the heart, PKC isoforms ,
ß1/2, , , and have been identified in
rat neonatal cardiomyocytes.8 In adult rat
cardiomyocytes and myocardium, PKC isoforms
and seem to be maintained with age, whereas other PKC isoforms may
decline.9 10 In human myocardium, PKC isoforms
, ß1/2,
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