Insulin-like growth factor-I rapidly activates multiple signal transduction pathways in cultured rat cardiac myocytes

Foncea, R; Sapag-Hagar, M; Lavandero S.; Andersson M.; Ketterman A.; Sugden P.H.; Blakesley V.; LeRoith, D

Keywords: proteins, growth, rat, enzyme, dna, activation, heart, animals, phosphorylation, synthesis, culture, rats, protein, cell, hypertrophy, tyrosine, transduction, signal, kinases, article, kinase, myocardium, factor, activity, group, controlled, ventricle, animal, c, phospholipase, study, 1, 3, priority, nonhuman, journal, Animalia, Rats,, Sprague-Dawley, Cells,, Cultured, Proto-Oncogene, I, Protein-Serine-Threonine, dependent, somatomedin, Insulin-Like, Phosphotransferases, (Alcohol, Acceptor), 1-Phosphatidylinositol, 3-Kinase, Ca(2+)-Calmodulin, Mitogen-Activated, c-raf


In response to insulin-like growth factor-I (IGF-I), neonatal rat cardiac myocytes exhibit a hypertrophic response. The elucidation of the IGF- I signal transduction system in these cells remains unknown. We show here that cardiac myocytes present a single class of high affinity receptors (12,446 ± 3,669 binding sites/cell) with a dissociation constant of 0.36 ± 0.10 nM. Two different ?-subunits of IGF-I receptor were detected, and their autophosphorylation was followed by increases in the phosphetyrosine content of extracellular signal-regulated kinases (ERKs), insulin receptor substrate 1, phospholipase C-?1, and phosphatidylinositol 3-kinase. IGF.I transiently activates c-Raf in cultured neonatal cardiac myocytes, whereas A-raf is activated much less than c-Raf. Two peaks of ERK activity (ERK1 and ERK2) were resolved in cardiac myocytes treated with IGF-I by fast protein liquid chromatography, both being stimulated by IGF-I (with EC50 values for the stimulation of ERK1 and ERK2 by IGF-I of 0.10 and 0.12 nM, respectively). Maximal activation of ERK2 (12-fold) and ERK1 (8.3-fold) activities was attained after a 5-min exposure to IGF-I. Maximal activation of p90 S6 kinase by IGF-I was achieved after 10 min, and then the activity decreased slowly. Interestingly, IGF-I stimulates incorporation of [3H]phenylalanine (1.6- fold) without any effect on [3H]thymidine incorporation. These data suggest that IGF-I activates multiple signal transduction pathways in cardiac myocytes some of which may be relevant to the hypertrophic response of the heart.

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Volumen: 272
Número: 31
Editorial: Elsevier
Fecha de publicación: 1997
Página de inicio: 19115
Página final: 19124