Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Turnover of the active fraction of IRS1 involves raptor-mTOR- and S6K1-dependent serine phosphorylation in cell culture models of tuberous sclerosis.

Molecular and cellular biology | 2006

The TSC1-TSC2/Rheb/Raptor-mTOR/S6K1 cell growth cassette has recently been shown to regulate cell autonomous insulin and insulin-like growth factor I (IGF-I) sensitivity by transducing a negative feedback signal that targets insulin receptor substrates 1 and 2 (IRS1 and -2). Using two cell culture models of the familial hamartoma syndrome, tuberous sclerosis, we show here that Raptor-mTOR and S6K1 are required for phosphorylation of IRS1 at a subset of serine residues frequently associated with insulin resistance, including S307, S312, S527, S616, and S636 (of human IRS1). Using loss- and gain-of-function S6K1 constructs, we demonstrate a requirement for the catalytic activity of S6K1 in both direct and indirect regulation of IRS1 serine phosphorylation. S6K1 phosphorylates IRS1 in vitro on multiple residues showing strong preference for RXRXXS/T over S/T,P sites. IRS1 is preferentially depleted from the high-speed pellet fraction in TSC1/2-deficient mouse embryo fibroblasts or in HEK293/293T cells overexpressing Rheb. These studies suggest that, through serine phosphorylation, Raptor-mTOR and S6K1 cell autonomously promote the depletion of IRS1 from specific intracellular pools in pathological states of insulin and IGF-I resistance and thus potentially in lesions associated with tuberous sclerosis.

Pubmed ID: 16914728 RIS Download

Research resources used in this publication

None found

Antibodies used in this publication

None found

Associated grants

  • Agency: NCI NIH HHS, United States
    Id: R01 CA082683
  • Agency: NCI NIH HHS, United States
    Id: CA82683
  • Agency: NIGMS NIH HHS, United States
    Id: GM67407
  • Agency: NCI NIH HHS, United States
    Id: CA14195
  • Agency: NCI NIH HHS, United States
    Id: T32-CA09523
  • Agency: NIGMS NIH HHS, United States
    Id: F32 GM067407
  • Agency: NCI NIH HHS, United States
    Id: T32 CA009523
  • Agency: NCI NIH HHS, United States
    Id: P30 CA014195

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


Salk Institute Razavi Newman Integrative Genomics and Bioinformatics Core Facility (IGC) (tool)

RRID:SCR_014842

Core facility established to assist the Salk community with integrating genomics data into their research. The primary focus of the core is to provide analysis support for next-generation sequencing applications.

View all literature mentions