About a Controversy Concerning the Existence of a Mitogen-Responsive S6-Kinase (Late-Eluting from Deae-Sephacel)

The capacity for skeletal muscle to recover its mass following periods of unloading (regrowth) has been reported to decline with age. Although the mechanisms responsible for the impaired regrowth are not known, it has been suggested that aged muscles have a diminished capacity to sense and subsequently respond to a given amount of mechanical stimuli (mechanosensitivity). To test this hypothesis, extensor digitorum longus muscles from young (2–3 mo) and old (26–27 mo) mice were subjected to intermittent 15% passive stretch (ex vivo) as a source of mechanical stimulation and analyzed for alterations in the phosphorylation of stress-activated protein kinase (p38), ribosomal S6 kinase (p70S6k), and the p54 jun N-terminal kinase (JNK2). The results indicated that the average magnitude of specific tension (mechanical stimuli) induced by 15% stretch was similar in muscles from young and old mice. Young and old muscles also revealed similar increases in the magnitude of mechanically induced p38, p70S6k (threonine/serine 421/424 and threonine 389), and JNK2 phosphorylation. In addition, coincubation experiments demonstrated that the release of locally acting growth factors was not sufficient for the induction of JNK2 phosphorylation, suggesting that JNK2 was activated by a mechanical rather than a mechanical/growth factor-dependent mechanism. Taken together, the results of this study demonstrate that aging does not alter the mechanosensitivity of the p38, p70S6k, and JNK2 signaling pathways in skeletal muscle.

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Monoclonal Antibodies Mimic Insulin Activation of Ribosomal Protein S6 Kinase without Activation of Insulin Receptor Tyrosine Kinase

Journal of Biological Chemistry ◽

10.1016/s0021-9258(19)47250-5 ◽

1989 ◽

Vol 264 (32) ◽

pp. 18951-18959 ◽

Cited By ~ 2

Author(s):

C K Sung ◽

B A Maddux ◽

D M Hawley ◽

I D Goldfine

Keyword(s):

Monoclonal Antibodies ◽

Tyrosine Kinase ◽

Ribosomal Protein ◽

Insulin Receptor ◽

Receptor Tyrosine Kinase ◽

S6 Kinase ◽

Insulin Receptor Tyrosine Kinase ◽

Ribosomal Protein S6 ◽

Ribosomal Protein S6 Kinase

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Role of PRAS40 in Akt and mTOR signaling in health and disease

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00660.2011 ◽

2012 ◽

Vol 302 (12) ◽

pp. E1453-E1460 ◽

Cited By ~ 92

Author(s):

Claudia Wiza ◽

Emmani B. M. Nascimento ◽

D. Margriet Ouwens

Keyword(s):

Mammalian Target Of Rapamycin ◽

Mtor Signaling ◽

Cellular Growth ◽

S6 Kinase ◽

Binding Partners ◽

Health And Disease ◽

Mtor Complex 1 ◽

Mtor Activity

The proline-rich Akt substrate of 40 kDa (PRAS40) acts at the intersection of the Akt- and mammalian target of rapamycin (mTOR)-mediated signaling pathways. The protein kinase mTOR is the catalytic subunit of two distinct signaling complexes, mTOR complex 1 (mTORC1) and mTORC2, that link energy and nutrients to the regulation of cellular growth and energy metabolism. Activation of mTOR in response to nutrients and growth factors results in the phosphorylation of numerous substrates, including the phosphorylations of S6 kinase by mTORC1 and Akt by mTORC2. Alterations in Akt and mTOR activity have been linked to the progression of multiple diseases such as cancer and type 2 diabetes. Although PRAS40 was first reported as substrate for Akt, investigations toward mTOR-binding partners subsequently identified PRAS40 as both component and substrate of mTORC1. Phosphorylation of PRAS40 by Akt and by mTORC1 itself results in dissociation of PRAS40 from mTORC1 and may relieve an inhibitory constraint on mTORC1 activity. Adding to the complexity is that gene silencing studies indicate that PRAS40 is also necessary for the activity of the mTORC1 complex. This review summarizes the regulation and potential function(s) of PRAS40 in the complex Akt- and mTOR-signaling network in health and disease.

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