Title

AKAP-Lbc enhances cyclic AMP control of the ERK1/2 cascade

UMMS Affiliation

Program in Molecular Medicine

Date

12-1-2010

Document Type

Article

Medical Subject Headings

A Kinase Anchor Proteins; Amino Acid Sequence; Animals; Cell Line; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Humans; *MAP Kinase Signaling System; Mice; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Molecular Sequence Data; Protein Kinases; Proto-Oncogene Proteins; Sequence Alignment

Disciplines

Biochemistry | Cell Biology | Cellular and Molecular Physiology | Molecular Biology

Abstract

Mitogen-activated protein kinase (MAPK) cascades propagate a variety of cellular activities. Processive relay of signals through RAF-MEK-ERK modulates cell growth and proliferation. Signalling through this ERK cascade is frequently amplified in cancers, and drugs such as sorafenib (which is prescribed to treat renal and hepatic carcinomas) and PLX4720 (which targets melanomas) inhibit RAF kinases. Natural factors that influence ERK1/2 signalling include the second messenger cyclic AMP. However, the mechanisms underlying this cascade have been difficult to elucidate. We demonstrate that the A-kinase-anchoring protein AKAP-Lbc and the scaffolding protein kinase suppressor of Ras (KSR-1) form the core of a signalling network that efficiently relay signals from RAF, through MEK, and on to ERK1/2. AKAP-Lbc functions as an enhancer of ERK signalling by securing RAF in the vicinity of MEK1 and synchronizing protein kinase A (PKA)-mediated phosphorylation of Ser 838 on KSR-1. This offers mechanistic insight into cAMP-responsive control of ERK signalling events.

Rights and Permissions

Citation: Nat Cell Biol. 2010 Dec;12(12):1242-9. doi: 10.1038/ncb2130. Epub 2010 Nov 21. Link to article on publisher's site

Related Resources

Link to Article in PubMed

PubMed ID

21102438