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

Rocio E Foncea Avila, Monica Andersson, Albert Ketterman, Vicky Blakesley, Mario Sapag-Hagar, Peter H. Sugden, Derek LeRoith, Sergio Lavandero

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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 β-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-γ1, 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.

Original languageEnglish (US)
Pages (from-to)19115-19124
Number of pages10
JournalJournal of Biological Chemistry
Issue number31
StatePublished - Aug 1 1997


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