Role of the Insulin-Like Growth Factor 1 (IGF1)/Phosphoinositide-3-Kinase (PI3K) Pathway Mediating Physiological Cardiac Hypertrophy

2008 ◽  
pp. 90-117 ◽  
Author(s):  
Julie R. McMullen ◽  
Seigo Izumo
Keyword(s):  
Growth Factor ◽  
Cardiac Hypertrophy ◽  
Pi3k Pathway ◽  
Insulin Like Growth Factor ◽  
Physiological Cardiac Hypertrophy ◽  
Phosphoinositide 3 Kinase

scholarly journals Deletion of Ribosomal S6 Kinases Does Not Attenuate Pathological, Physiological, or Insulin-Like Growth Factor 1 Receptor-Phosphoinositide 3-Kinase-Induced Cardiac Hypertrophy

2004 ◽  
Vol 24 (14) ◽  
pp. 6231-6240 ◽  
Author(s):  
Julie R. McMullen ◽  
Tetsuo Shioi ◽  
Li Zhang ◽  
Oleg Tarnavski ◽  
Megan C. Sherwood ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transgenic Mice ◽  
Cardiac Hypertrophy ◽  
Physiological Stress ◽  
Pi3k Pathway ◽  
Insulin Like Growth Factor ◽  
Cardiac Phenotype ◽  
Heart Size ◽  
Phosphoinositide 3 Kinase ◽  
Igf1 Receptor

ABSTRACT Ribosomal S6 kinases (S6Ks) have been depicted as critical effectors downstream of growth factor pathways, which play an important role in the regulation of protein synthesis by phosphorylating the ribosomal protein, S6. The goal of this study was to determine whether S6Ks regulate heart size, are critical for the induction of cardiac hypertrophy in response to a pathological or physiological stimulus, and whether S6Ks are critical downstream effectors of the insulin-like growth factor 1 (IGF1)-phosphoinositide 3-kinase (PI3K) pathway. For this purpose, we generated and characterized cardiac-specific S6K1 and S6K2 transgenic mice and subjected S6K1−/−, S6K2−/−, and S6K1−/− S6K2−/− mice to a pathological stress (aortic banding) or a physiological stress (exercise training). To determine the genetic relationship between S6Ks and the IGF1-PI3K pathway, S6K transgenic and knockout mice were crossed with cardiac-specific transgenic mice overexpressing the IGF1 receptor (IGF1R) or PI3K mutants. Here we show that overexpression of S6K1 induced a modest degree of hypertrophy, whereas overexpression of S6K2 resulted in no obvious cardiac phenotype. Unexpectedly, deletion of S6K1 and S6K2 had no impact on the development of pathological, physiological, or IGF1R-PI3K-induced cardiac hypertrophy. These studies suggest that S6Ks alone are not essential for the development of cardiac hypertrophy.

scholarly journals Polycystin-1 is required for insulin-like growth factor 1-induced cardiomyocyte hypertrophy

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255452
Author(s):  
Carolina Fernández ◽  
Natalia Torrealba ◽  
Francisco Altamirano ◽  
Valeria Garrido-Moreno ◽  
César Vásquez-Trincado ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cardiac Hypertrophy ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Pressure Overload ◽  
Cardiomyocyte Hypertrophy ◽  
Protein Tyrosine Phosphatase 1B ◽  
Insulin Like Growth Factor ◽  
Protein Tyrosine

Cardiac hypertrophy is the result of responses to various physiological or pathological stimuli. Recently, we showed that polycystin-1 participates in cardiomyocyte hypertrophy elicited by pressure overload and mechanical stress. Interestingly, polycystin-1 knockdown does not affect phenylephrine-induced cardiomyocyte hypertrophy, suggesting that the effects of polycystin-1 are stimulus-dependent. In this study, we aimed to identify the role of polycystin-1 in insulin-like growth factor-1 (IGF-1) signaling in cardiomyocytes. Polycystin-1 knockdown completely blunted IGF-1-induced cardiomyocyte hypertrophy. We then investigated the molecular mechanism underlying this result. We found that polycystin-1 silencing impaired the activation of the IGF-1 receptor, Akt, and ERK1/2 elicited by IGF-1. Remarkably, IGF-1-induced IGF-1 receptor, Akt, and ERK1/2 phosphorylations were restored when protein tyrosine phosphatase 1B was inhibited, suggesting that polycystin-1 knockdown deregulates this phosphatase in cardiomyocytes. Moreover, protein tyrosine phosphatase 1B inhibition also restored IGF-1-dependent cardiomyocyte hypertrophy in polycystin-1-deficient cells. Our findings provide the first evidence that polycystin-1 regulates IGF-1-induced cardiomyocyte hypertrophy through a mechanism involving protein tyrosine phosphatase 1B.

scholarly journals Early origins of heart disease: Low birth weight and the role of the insulin-like growth factor system in cardiac hypertrophy

2012 ◽  
Vol 39 (11) ◽  
pp. 958-964 ◽  
Author(s):  
Kimberley CW Wang ◽  
Kimberley J Botting ◽  
Monalisa Padhee ◽  
Song Zhang ◽  
I Caroline McMillen ◽  
...  
Keyword(s):  
Heart Disease ◽  
Birth Weight ◽  
Growth Factor ◽  
Low Birth Weight ◽  
Cardiac Hypertrophy ◽  
Insulin Like Growth Factor ◽  
Factor System

The Role of the Insulin-like Growth Factor-I Receptor in Cancer

1995 ◽  
Vol 766 (1 Receptor Acti) ◽  
pp. 402-408 ◽  
Author(s):  
D. LEROITH ◽  
H. WERNER ◽  
S. NEUENSCHWANDER ◽  
T. KALEBIC ◽  
L. J. HELMAN
Keyword(s):  
Growth Factor ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Growth Factor I
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