Title

Contingent phosphorylation/dephosphorylation provides a mechanism of molecular memory in WASP

UMMS Affiliation

Program in Gene Function and Expression; Program in Molecular Medicine

Date

5-2003

Document Type

Article

Medical Subject Headings

Actin-Related Protein 2; Actin-Related Protein 3; Cytoskeletal Proteins; Eukaryotic Cells; Humans; Molecular Structure; Phosphorylation; Protein Binding; Protein Structure, Tertiary; Proteins; Signal Transduction; Wiskott-Aldrich Syndrome Protein; cdc42 GTP-Binding Protein; src-Family Kinases

Disciplines

Cellular and Molecular Physiology | Genetics and Genomics | Molecular Biology

Abstract

Cells can retain information about previous stimuli to produce distinct future responses. The biochemical mechanisms by which this is achieved are not well understood. The Wiskott-Aldrich syndrome protein (WASP) is an effector of the Rho-family GTPase Cdc42, whose activation leads to stimulation of the actin nucleating assembly, Arp2/3 complex. We demonstrate that efficient phosphorylation and dephosphorylation of WASP at Y291 are both contingent on binding to activated Cdc42. Y291 phosphorylation increases the basal activity of WASP toward Arp2/3 complex and enables WASP activation by new stimuli, SH2 domains of Src-family kinases. The requirement for contingency in both phosphorylation and dephosphorylation enables long-term storage of information by WASP following decay of GTPase signals. This biochemical circuitry allows WASP to respond to the levels and timing of GTPase and kinase signals. It provides mechanisms to specifically achieve transient or persistent actin remodeling, as well as long-lasting potentiation of actin-based responses to kinases.

Rights and Permissions

Citation: Mol Cell. 2003 May;11(5):1215-27. DOI 10.1016/S1097-2765(03)00139-4

Comments

At the time of publication, Eduardo Torres was not yet affiliated with the University of Massachusetts Medical School.

Related Resources

Link to Article in PubMed

PubMed ID

12769846