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

Robert A. Frost, Charles H. Lang

Research output: Contribution to journalReview article

122 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)378-387
Number of pages10
JournalJournal of applied physiology
Volume103
Issue number1
DOIs
StatePublished - Jul 1 2007

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Proto-Oncogene Proteins c-akt
Intercellular Signaling Peptides and Proteins
Cytokines
Muscles
Skeletal Muscle
Myostatin
Food
Muscle Proteins
Insulin-Like Growth Factor I
Protein Kinases
Hypertrophy
Interleukin-6
Tumor Necrosis Factor-alpha
Phosphorylation
Nexus
Hormones
Amino Acids
Glucose

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)

Cite this

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Protein kinase B/Akt : A nexus of growth factor and cytokine signaling in determining muscle mass. / Frost, Robert A.; Lang, Charles H.

In: Journal of applied physiology, Vol. 103, No. 1, 01.07.2007, p. 378-387.

Research output: Contribution to journalReview article

TY - JOUR

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AB - 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.

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