doi: 10.1161/CIRCRESAHA.108.173807
© 2008 American Heart Association, Inc.
Editorials |
PICOT
A Multidomain Scaffolding Inhibitor of Hypertrophic Signal Transduction
From the Cardiovascular Institute, Loyola University Chicago, Stritch School of Medicine, Maywood, Ill.
Correspondence to Allen M. Samarel, MD, Cardiovascular Institute, Loyola University Medical Center, 2160 S 1st Ave, Maywood, IL 60153. E-mail asamare@lumc.edu
See related article, pages 711–719
Key Words: protein kinase C • calcineurin • muscle LIM protein • mechanotransduction
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
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Introduction |
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Unlike the explosive hyperplastic growth that occurs during early embryonic development, neonatal and adult cardiomyocytes undergo hypertrophy as a consequence of a much more subtle increase in the fractional growth rate of the heart. Both physiological and pathological hypertrophy results from mechanical and neurohormonal signals (and their downstream effectors) that tend to increase the rate of cardiac protein synthesis. These growth-promoting pathways are counterbalanced by signaling molecules that tend to inhibit or attenuate the prohypertrophic growth response.1 In this issue of Circulation Research, Jeong et al2 continue to add to a growing list of negative regulators of cardiomyocyte hypertrophy, and describe how PICOT (protein kinase C–interacting cousin of thioredoxin) may function to inhibit the calcineurin (CnA)–nuclear factor of activated T cells (NFAT) signaling pathway responsible for regulating specific aspects of the hypertrophic phenotype.
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PICOT Is a Multidomain Scaffolding Inhibitor of Protein Kinase C-
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PICOT was first identified in 2000 by Witte et al in a yeast 2-hybrid screen of protein kinase C (PKC)
-interacting proteins.3 These authors used full-length, catalytically inactive PKC to screen a Jurkat T-cell lymphoma cDNA library. They identified a highly conserved, 37.5-kDa cytoplasmic protein containing at least 2 functional domains. The N-terminal, PKC binding domain shared sequence homology with the thioredoxin family of proteins but lacked the conserved Cys-Gly-Pro-Cys motif essential for enzyme activity. The C-terminal domain contained 2 tandem repeats, now called PICOT homology (PIH) domains that are shared by proteins expressed in a diverse group of organisms. PICOT formed a protein complex with PKC (but not PKC
) in vitro and in living
Related Article:
Circ. Res. 2008 102: 711-719.