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(Received for publication, March 10, 1997, and in revised form, May 8, 1997)
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From the 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 Departamento de Bioquímica y
Biología Molecular, Facultad Ciencias Químicas y
Farmacéuticas, Universidad de Chile, Olivos 1007, Santiago,
Chile, the ¶ Division of Cardiac Medicine, Imperial College School
of Medicine, National Heart and Lung Institute, London SW3 6LY, United
Kingdom, and the ** Diabetes Branch, NIDDK, National Institutes of
Health, Bethesda, Maryland 20892-1770
-subunits of IGF-I receptor were
detected, and their autophosphorylation was followed by increases in
the phosphotyrosine 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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Y. Zhang, S. Zhong, Z. Dong, N. Chen, A. M. Bode, W.-y. Ma, and Z. Dong UVA Induces Ser381 Phosphorylation of p90RSK/MAPKAP-K1 via ERK and JNK Pathways J. Biol. Chem., April 27, 2001; 276(18): 14572 - 14580. [Abstract] [Full Text] [PDF]
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Y. Zhang, Z. Dong, M. Nomura, S. Zhong, N. Chen, A. M. Bode, and Z. Dong Signal Transduction Pathways Involved in Phosphorylation and Activation of p70S6K Following Exposure to UVA Irradiation J. Biol. Chem., June 8, 2001; 276(24): 20913 - 20923. [Abstract] [Full Text] [PDF]
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J. F. Kuemmerle and K. S. Murthy Coupling of the Insulin-like Growth Factor-I Receptor Tyrosine Kinase to Gi2 in Human Intestinal Smooth Muscle. Gbeta gamma -DEPENDENT MITOGEN-ACTIVATED PROTEIN KINASE ACTIVATION AND GROWTH J. Biol. Chem., March 2, 2001; 276(10): 7187 - 7194. [Abstract] [Full Text] [PDF]
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C. Lu, G. Schwartzbauer, M. A. Sperling, S. U. Devaskar, S. Thamotharan, P. D. Robbins, C. F. McTiernan, J.-L. Liu, J. Jiang, S. J. Frank, et al. Demonstration of Direct Effects of Growth Hormone on Neonatal Cardiomyocytes J. Biol. Chem., June 15, 2001; 276(25): 22892 - 22900. [Abstract] [Full Text] [PDF]
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