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The Ras‐interacting protein Rlf selectively regulates insulin signaling in cardiomyocytes
Author(s) -
AllenKlee Leah,
Post Ginell,
Post Steven
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a691-c
Subject(s) - phosphorylation , insulin , insulin receptor , protein kinase b , insulin receptor substrate , microbiology and biotechnology , signal transduction , guanine nucleotide exchange factor , mapk/erk pathway , cardioprotection , tyrosine phosphorylation , irs1 , biology , chemistry , medicine , endocrinology , insulin resistance , ischemia
Studies in cell culture, animal models, and humans indicate a role for insulin in cardioprotection. The cardioprotective effects of insulin are mediated, in part, by the activation of Ras‐dependent signaling cascades. We previously identified the Ral guanine nucleotide exchange factor‐like factor (Rlf) as a Ras‐interacting protein that differentially regulates Ras signaling in cardiomyocytes. To study the role of Rlf in insulin‐mediated signal transduction in cardiomyocytes, we overexpressed Rlf using an adenoviral vector in neonatal rat ventricular myocytes (NRVMs) and examined insulin‐mediated AKT, ERK, and JNK activation. Although Rlf overexpression had no effect on basal kinase activity or on ERK phosphorylation, Rlf enhanced insulin‐induced PI3‐kinase activation (AKT phosphorylation). In contrast, Rlf overexpression attenuated insulin‐induced JNK phosphorylation. JNK is known to negatively regulate insulin signal transduction by serine phosphorylation of the Insulin Receptor Substrate (IRS) thereby inhibiting its interaction with the insulin receptor. Consistent with its inhibitory effect on JNK activation, Rlf overexpression enhanced insulin‐induced tyrosine phosphorylation of IRS. Together, these results identify a novel interaction between Rlf and insulin signaling pathways and suggest that Rlf augments insulin‐mediated cardioprotection. Research support provided by the NIH.