New mechanisms in heptahelical receptor signaling to mitogen activated protein kinase cascades.

Published

Journal Article (Review)

Activation of classical second messenger cascades cannot fully explain the recently appreciated roles of heptahelical, or G-protein coupled receptors (GPCRs), in stimulation of mitogen activated protein kinase (MAPK) cascades. Rather, several distinct signaling mechanisms appear to contribute to GPCR-mediated MAPK activation. These include transactivation of the Epidermal Growth Factor Receptor (EGFR) via the autocrine/paracrine release of EGF-like ligands at the cell surface and scaffolding of MAPK cascades. A significant advance in the understanding of how GPCRs activate MAPK cascades is the discovery that beta-arrestin, a protein well known for its roles in both receptor desensitization and internalization, serves as a scaffolding protein for at least two GPCR stimulated MAPK cascades, the extracellular signal regulated kinase (ERK) cascade and the c-jun N-terminal kinase 3 (JNK3) cascade. Together, these novel mechanisms of GPCR-mediated MAPK regulation may permit GPCRs in specific situations to control the temporal and spatial activity of MAPKs and thereby determine the consequences of GPCR stimulation with respect to transcriptional activation, cell proliferation and apoptosis.

Full Text

Duke Authors

Cited Authors

  • Pierce, KL; Luttrell, LM; Lefkowitz, RJ

Published Date

  • March 26, 2001

Published In

Volume / Issue

  • 20 / 13

Start / End Page

  • 1532 - 1539

PubMed ID

  • 11313899

Pubmed Central ID

  • 11313899

International Standard Serial Number (ISSN)

  • 0950-9232

Digital Object Identifier (DOI)

  • 10.1038/sj.onc.1204184

Language

  • eng

Conference Location

  • England