Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

The CREB coactivator TORC2 functions as a calcium- and cAMP-sensitive coincidence detector

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Screaton, R. A.
  • Conkright, Michael
  • Katoh, Y.
  • Best, J. L.
  • Canettieri, G.
  • Jeffries, S.
  • Guzman, E.
  • Niessen, Sherry
  • Yates III, John
  • Takemori, H.
  • Okamoto, M.
  • Montminy, M.

publication date

  • October 2004

journal

  • Cell  Journal

abstract

  • Elevations in circulating glucose and gut hormones during feeding promote pancreatic islet cell viability in part via the calcium- and cAMP-dependent activation of the transcription factor CREB. Here, we describe a signaling module that mediates the synergistic effects of these pathways on cellular gene expression by stimulating the dephosphorylation and nuclear entry of TORC2, a CREB coactivator. This module consists of the calcium-regulated phosphatase calcineurin and the Ser/Thr kinase SIK2, both of which associate with TORC2. Under resting conditions, TORC2 is sequestered in the cytoplasm via a phosphorylation-dependent interaction with 14-3-3 proteins. Triggering of the calcium and cAMP second messenger pathways by glucose and gut hormones disrupts TORC2:14-3-3 complexes via complementary effects on TORC2 dephosphorylation; calcium influx increases calcineurin activity, whereas cAMP inhibits SIK2 kinase activity. Our results illustrate how a phosphatase/kinase module connects two signaling pathways in response to nutrient and hormonal cues.

subject areas

  • 14-3-3 Proteins
  • Active Transport, Cell Nucleus
  • Animals
  • Calcineurin
  • Calcium
  • Calcium Signaling
  • Cell Line
  • Cyclic AMP
  • Cyclic AMP Response Element-Binding Protein
  • Gene Expression Regulation
  • Glucose
  • Hormones
  • Humans
  • Islets of Langerhans
  • Macromolecular Substances
  • Mice
  • Phosphoproteins
  • Phosphorylation
  • Protein-Serine-Threonine Kinases
  • RNA, Small Interfering
  • Signal Transduction
  • Trans-Activators
  • Transcription Factors
scroll to property group menus

Identity

International Standard Serial Number (ISSN)

  • 0092-8674

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2004.09.015

PubMed ID

  • 15454081
scroll to property group menus

Additional Document Info

start page

  • 61

end page

  • 74

volume

  • 119

issue

  • 1

©2021 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support