Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2007 Mar 9;282(10):6946-53.
doi: 10.1074/jbc.M608338200. Epub 2007 Jan 17.

SHP-2 Regulates Cell Growth by Controlling the mTOR/S6 Kinase 1 Pathway

Affiliations
Free article

SHP-2 Regulates Cell Growth by Controlling the mTOR/S6 Kinase 1 Pathway

Christina I Zito et al. J Biol Chem. .
Free article

Abstract

Cell growth (accumulation in cell mass) ensues through the promotion of macromolecular biosynthesis. S 6 ribosomal kinase 1 (S6K1), which is activated by the mammalian target of rapamycin, is critical for cell growth. The early events that control S6K1 signaling remain unclear. Here we show that SHP-2 suppresses S6K1 activity under conditions of growth factor deprivation. We show that under conditions of growth factor deprivation, S6K1 activity was increased in fibroblasts lacking functional SHP-2 and in cells where knock down of SHP-2 expression was established by small interference RNA. Consistent with these findings, fibroblasts lacking functional SHP-2 exhibited increased cell size as compared with wild type cells. Growth factor deprivation reduces cellular energy, and the energy-sensing 5'-AMP-activated protein kinase (AMPK) negatively regulates S6K1. We found that SHP-2 promoted AMPK activity under conditions of growth factor deprivation (low energy), suggesting that SHP-2 negatively regulates S6K1 via an AMPK-dependent pathway. These results implicate SHP-2 as an early mediator in the S6K1 signaling pathway to limit cell growth in low energy states.

Similar articles

See all similar articles

Cited by 6 articles

See all "Cited by" articles

Publication types

MeSH terms

Substances

LinkOut - more resources

Feedback