Department of Anesthesiology

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

TitlePhosphorylation of spinophilin by ERK and cyclin-dependent PK 5 (Cdk5).
Publication TypeJournal Article
Year of Publication2005
AuthorsFutter M, Uematsu K, Bullock SA, Kim Y, Hemmings HC, Nishi A, Greengard P, Nairn AC
JournalProc Natl Acad Sci U S A
Volume102
Issue9
Pagination3489-94
Date Published2005 Mar 1
ISSN0027-8424
KeywordsActins, Animals, Cell Line, Cyclin-Dependent Kinase 5, Cyclin-Dependent Kinases, Hippocampus, Humans, Immunohistochemistry, Male, Mice, Mice, Inbred C57BL, Microfilament Proteins, Mitogen-Activated Protein Kinase 1, Morphogenesis, Nerve Tissue Proteins, Neurons, Peptide Mapping, Phosphorylation, Protein Binding
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.

DOI10.1073/pnas.0409802102
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID15728359
PubMed Central IDPMC552943
Grant ListDA1044 / DA / NIDA NIH HHS / United States
MH40899 / MH / NIMH NIH HHS / United States
P01 DA010044 / DA / NIDA NIH HHS / United States