Phosphorylation of spinophilin by ERK and cyclin-dependent PK 5 (Cdk5)

Marie Futter, Ken Uematsu, Stewart A. Bullock, Yong Kim, Hugh C. Hemmings, Akinori Nishi, Paul Greengard, Angus C. Nairn

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Spinophilin is a protein that binds to protein phosphatase-1 and actin and modulates excitatory synaptic transmission and dendritic spine morphology. We have identified three sites phosphorylated by ERK2 (Ser-15 and Ser-205) and cyclin-dependent PK 5 (Cdk5) (Ser-17), within the actin-binding domain of spinophilin. Cdk5 and ERK2 both phosphorylated spinophilin in intact cells. However, in vitro, phosphorylation by ERK2, but not by Cdk5, was able to modulate the ability of spinophilin to bind to and bundle actin filaments. In neurons and HEK293 cells expressing GFP-tagged variants of spinophilin, imaging studies demonstrated that introduction of a phospho-site mimic (Ser-15 to glutamate) was associated with increased filopodial density. These results support a role for spinophilin phosphorylation by ERK2 in the regulation of spine morphogenesis.

Original languageEnglish (US)
Pages (from-to)3489-3494
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number9
DOIs
StatePublished - Mar 1 2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Actin
  • Dendritic spines
  • Protein phosphatase

Fingerprint

Dive into the research topics of 'Phosphorylation of spinophilin by ERK and cyclin-dependent PK 5 (Cdk5)'. Together they form a unique fingerprint.

Cite this