scholarly journals Protein kinase B/Akt: a nexus of growth factor and cytokine signaling in determining muscle mass

2007 ◽  
Vol 103 (1) ◽  
pp. 378-387 ◽  
Author(s):  
Robert A. Frost ◽  
Charles H. Lang
Keyword(s):  
Skeletal Muscle ◽  
Growth Factors ◽  
Growth Factor ◽  
Protein Kinase ◽  
Muscle Mass ◽  
Muscle Protein ◽  
Contractile Activity ◽  
Protein Kinase B ◽  
Muscle Size ◽  
Cytokine Signaling

Although the boundaries of skeletal muscle size are fundamentally determined by genetics, this dynamic tissue also demonstrates great plasticity in response to environmental and hormonal factors. Recent work indicates that contractile activity, nutrients, growth factors, and cytokines all contribute to determining muscle mass. Muscle responds not only to endocrine hormones but also to the autocrine production of growth factors and cytokines. Skeletal muscle synthesizes anabolic growth factors such as insulin-like growth factor (IGF)-I and potentially inhibitory cytokines such as interleukin (IL)-6, tumor necrosis factor (TNF)-α, and myostatin. These self-regulating inputs in turn influence muscle metabolism, including the use of nutrients such as glucose and amino acids. These changes are principally achieved by altering the activity of the protein kinase known as protein kinase B or Akt. Akt plays a central role in integrating anabolic and catabolic responses by transducing growth factor and cytokine signals via changes in the phosphorylation of its numerous substrates. Activation of Akt stimulates muscle hypertrophy and antagonizes the loss of muscle protein. Here we review the many signals that funnel through Akt to alter muscle mass.

Viral expression of insulin-like growth factor-I isoforms promotes different responses in skeletal muscle

2006 ◽  
Vol 100 (6) ◽  
pp. 1778-1784 ◽  
Author(s):  
Elisabeth R. Barton
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Muscle Mass ◽  
Muscle Hypertrophy ◽  
Muscle Development ◽  
Muscle Size ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Insulin-like growth factor I (IGF-I) is a critical protein for skeletal muscle development and regeneration. Its ability to promote skeletal muscle hypertrophy has been demonstrated by several methods. Alternative splicing of the Igf-1 gene does not affect the mature IGF-I protein but does produce different E peptide extensions, which have been reported to modify the potency of IGF-I. Viral-mediated delivery of murine IGF-IA and IGF-IB into skeletal muscle of 2-wk-old and 6-mo-old mice was utilized to compare the effects of the isoforms on muscle mass. In young mice, tissue content of IGF-I protein was significantly higher in rAAV-treated muscles than control muscles at 1, 2, and 4 mo postinjection. Viral injection of IGF-IB produced two- to sevenfold more IGF-I than rAAVIGF-IA. Hypertrophy was observed 2 and 4 mo postinjection, where both rAAVIGF-IA and rAAVIGF-IB were equally effective in increasing muscle mass. These results suggest that there is a threshold of IGF-I production necessary to promote muscle hypertrophy in young growing animals regardless of isoform. In 6-mo-old animals, only rAAVIGF-IA produced significant increases in muscle size, even though increased IGF-I content was observed after injection of both isoforms. Therefore, the ability for IGF-IB to promote muscle hypertrophy is only effective in growing animals, suggesting that the bioavailability of this isoform or its receptor affinity diminishes with age.

scholarly journals Phosphatidylinositol 3-kinase, protein kinase B and ribosomal S6 kinases in the stimulation of thyroid epithelial cell proliferation by cAMP and growth factors in the presence of insulin

2000 ◽  
Vol 348 (2) ◽  
pp. 351-358 ◽  
Author(s):  
Katia COULONVAL ◽  
Fabrice VANDEPUT ◽  
Rob C. STEIN ◽  
Sara C. KOZMA ◽  
Françoise LAMY ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Protein Kinase ◽  
Dna Synthesis ◽  
Protein Kinase B ◽  
Phosphatidylinositol 3 Kinase ◽  
S6 Kinase ◽  
P70 S6 Kinase ◽  
Stimulation Of ◽  
Phosphatidylinositol 3

The proliferation of most normal cells depends on the co-operation of several growth factors and hormones, each with a specific role, but the key events involved in the action of each necessary stimulant remain largely uncharacterized. In the present study, the pathways involved in the mechanism(s) of co-operation have been investigated in primary cultures of dog thyroid epithelial cells. In this physiologically relevant system, thyroid stimulating hormone (TSH) acting through cAMP, epidermal growth factor (EGF) and phorbol esters (such as PMA) induce DNA synthesis. Their effect requires stimulation of the insulin-like growth factor-1 (IGF-1) receptor by either IGF-1 or insulin, which are not themselves mitogenic agents. In contrast, hepatocyte growth factor (HGF) is itself fully mitogenic. The results of the study demonstrate that cAMP, EGF, HGF and PMA stimulate p70 ribosomal S6 kinase (p70 S6 kinase). However, insulin/IGF-1 also stimulate p70 S6 kinase. Thus stimulation of p70 S6 kinase might be necessary, but is certainly not sufficient, for the induction of DNA synthesis and is not specific for any stimulated pathway. In contrast, phosphatidylinositol 3-kinase (PI 3-kinase) and protein kinase B (PKB) activation by insulin and HGF is strong and sustained, whereas it is weak and transient with EGF and absent in the presence of TSH or PMA. These findings suggest that: (i) stimulation of PI 3-kinases and/or PKB is not involved in the cAMP-dependent pathways leading to thyrocyte proliferation, or in the action of PMA, (ii) the stimulation of the PI 3-kinase/PKB pathway may account for the permissive action of insulin/IGF-1 in the proliferation of these cells, and (iii) the stimulation of this pathway by HGF may explain why this agent does not require insulin or IGF-1 for its mitogenic action.

scholarly journals Protein Kinase B Activation and Lamellipodium Formation Are Independent Phosphoinositide 3-Kinase-Mediated Events Differentially Regulated by Endogenous Ras

1998 ◽  
Vol 18 (4) ◽  
pp. 1802-1811 ◽  
Author(s):  
David H. J. van Weering ◽  
Johan de Rooij ◽  
Barbara Marte ◽  
Julian Downward ◽  
Johannes L. Bos ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Protein Kinase ◽  
Egf Receptor ◽  
Protein Kinase B ◽  
Ectopic Expression ◽  
Differential Sensitivity ◽  
Phosphorylated Proteins ◽  
Phosphoinositide 3 Kinase

ABSTRACT Regulation of phosphoinositide 3-kinase (PI 3-kinase) can occur by binding of the regulatory p85 subunit to tyrosine-phosphorylated proteins and by binding of the p110 catalytic subunit to activated Ras. However, the way in which these regulatory mechanisms act to regulate PI 3-kinase in vivo is unclear. Here we show that several growth factors (basic fibroblast growth factor [bFGF], platelet-derived growth factor [PDGF], and epidermal growth factor [EGF; to activate an EGF receptor-Ret chimeric receptor]) all activate PI 3-kinase in vivo in the neuroectoderm-derived cell line SKF5. However, these growth factors differ in their ability to activate PI 3-kinase-dependent signaling. PDGF and EGF(Ret) treatment induced PI 3-kinase-dependent lamellipodium formation and protein kinase B (PKB) activation. In contrast, bFGF did not induce lamellipodium formation but activated PKB, albeit to a small extent. PDGF and EGF(Ret) stimulation resulted in binding of p85 to tyrosine-phosphorylated proteins and strong Ras activation. bFGF, however, induced only strong activation of Ras. In addition, while RasAsn17 abolished bFGF activation of PKB, PDGF- and EGF(Ret)-induced PKB activation was only partially inhibited and lamellipodium formation was unaffected. Interestingly, in contrast to activation of only endogenous Ras (bFGF), ectopic expression of activated Ras did result in lamellipodium formation. From this we conclude that, in vivo, p85 and Ras synergize to activate PI 3-kinase and that strong activation of only endogenous Ras exerts a small effect on PI 3-kinase activity, sufficient for PKB activation but not lamellipodium formation. This differential sensitivity to PI 3-kinase activation could be explained by our finding that PKB activation and lamellipodium formation are independent PI 3-kinase-induced events.

Signals mediating skeletal muscle remodeling by resistance exercise: PI3-kinase independent activation of mTORC1

2011 ◽  
Vol 110 (2) ◽  
pp. 561-568 ◽  
Author(s):  
Andrew Philp ◽  
D. Lee Hamilton ◽  
Keith Baar
Keyword(s):  
Skeletal Muscle ◽  
Growth Factors ◽  
Growth Factor ◽  
Resistance Exercise ◽  
Muscle Growth ◽  
Mammalian Target Of Rapamycin ◽  
Membrane Receptors ◽  
Muscle Size ◽  
Growth Factor Signaling ◽  
Independent Manner

For over 10 years, we have known that the activation of the mammalian target of rapamycin complex 1 (mTORC1) has correlated with the increase in skeletal muscle size and strength that occurs following resistance exercise. Initial cell culture and rodent models of muscle growth demonstrated that the activation of mTORC1 is common to hypertrophy induced by growth factors and increased loading. The further observation that high loads increased the local production of growth factors led to the paradigm that resistance exercise stimulates the autocrine production of factors that act on membrane receptors to activate mTORC1, and this results in skeletal muscle hypertrophy. Over the last few years, there has been a paradigm shift. From both human and rodent studies, it has become clear that the phenotypic and molecular responses to resistance exercise occur in a growth factor-independent manner. Although the mechanism of load-induced mTORC1 activation remains to be determined, it is clear that it does not require classical growth factor signaling.

A role for the actin cytoskeleton in the hormonal and growth-factor-mediated activation of protein kinase B

2001 ◽  
Vol 353 (3) ◽  
pp. 735
Author(s):  
K. PEYROLLIER ◽  
E. HAJDUCH ◽  
A. GRAY ◽  
G. J. LITHERLAND ◽  
A. R. PRESCOTT ◽  
...  
Keyword(s):  
Growth Factor ◽  
Protein Kinase ◽  
Actin Cytoskeleton ◽  
Protein Kinase B

ATP (Mg2+) induced inhibition of cyclic AMP reactivity with a skeletal muscle protein kinase

1972 ◽  
Vol 47 (4) ◽  
pp. 653-661 ◽  
Author(s):  
Mari K. Haddox ◽  
Nancy E. Newton ◽  
Diane K. Hartle ◽  
Nelson D. Goldberg
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Muscle Protein ◽  
Skeletal Muscle Protein
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