Molecular Pathways Insulin Receptor Substrate Regulation of Phosphoinositide 3-Kinase

نویسندگان

  • Heather E. Metz
  • A. McGarry Houghton
چکیده

Insulin receptor substrates (IRS) serve as downstreammessengers from activated cell surface receptors to numerous signaling pathway cascades. One of these pathways, phosphoinositide 3-kinase (PI3K), frequently displays aberrant function in the setting of cancer. IRS proteins are capable of both regulating and activating PI3K, depending on the cell of origin. As such, both prohost and protumor functions have been described for IRS proteins in human cancers. IRS proteins may eventually serve as biomarkers of PI3K activity, and serve a much-needed role as a guide to using targeted pathway therapy. Additionally, IRS-1 could be indirectly targeted in lung cancer, by inhibiting neutrophil elastase, which functions to degrade IRS-1 in lung tumor cells, thereby generating PI3K hyperactivity. Clin Cancer Res; 17(2); 206–11. 2010 AACR.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Insulin receptor substrate-1 and phosphoinositide-dependent kinase-1 are required for insulin-stimulated production of nitric oxide in endothelial cells.

Vasodilator actions of insulin are mediated by signaling pathways involving phosphatidylinositol 3-kinase (PI 3-kinase) and Akt that lead to activation of endothelial nitric oxide synthase (eNOS) in endothelium. Signaling molecules immediately upstream and downstream from PI 3-kinase involved with production of NO in response to insulin have not been previously identified. In this study, we eva...

متن کامل

Reduced expression of the murine p85alpha subunit of phosphoinositide 3-kinase improves insulin signaling and ameliorates diabetes.

A critical component of insulin action is the enzyme phosphoinositide (PI) 3-kinase. The major regulatory subunits of PI 3-kinase, p85alpha and its splice variants, are encoded by the Pik3r1 gene. Heterozygous disruption of Pik3r1 improves insulin signaling and glucose homeostasis in normal mice and mice made insulin-resistant by heterozygous deletion of the Insulin receptor and/or insulin rece...

متن کامل

Progesterone receptor-B regulation of insulin-like growth factor-stimulated cell migration in breast cancer cells via insulin receptor substrate-2.

Progesterone action contributes to the signaling of many growth factor pathways relevant to breast cancer tumor biology, including the insulin-like growth factor (IGF) system. Previous work has shown that insulin receptor substrate-2 (IRS-2) but not IRS-1 levels were regulated by progestin in progesterone receptor-B (PR-B) isoform expressing MCF-7 cells (C4-12 PR-B). Furthermore, type 1 IGF rec...

متن کامل

Insulin receptor substrate regulation of phosphoinositide 3-kinase.

Insulin receptor substrates (IRS) serve as downstream messengers from activated cell surface receptors to numerous signaling pathway cascades. One of these pathways, phosphoinositide 3-kinase (PI3K), frequently displays aberrant function in the setting of cancer. IRS proteins are capable of both regulating and activating PI3K, depending on the cell of origin. As such, both prohost and protumor ...

متن کامل

Gelidium elegans Extract Ameliorates Type 2 Diabetes via Regulation of MAPK and PI3K/Akt Signaling

Gelidium elegans, a red alga native to the Asia Pacific region, contains biologically active polyphenols. We conducted a molecular biological study of the anti-diabetic effect of Gelidium elegans extract (GEE) in C57BL/KsJ-db/db mice. Mice that had been administered GEE had significantly lower body mass, water consumption, and fasting blood glucose than db/db controls. Moreover, hemoglobin A1c ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره   شماره 

صفحات  -

تاریخ انتشار 2011