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

doi:10.1073/pnas.0409802102

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 journal › Article › peer-review

48 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 language	English (US)
Pages (from-to)	3489-3494
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	102
Issue number	9
DOIs	https://doi.org/10.1073/pnas.0409802102
State	Published - Mar 1 2005
Externally published	Yes

All Science Journal Classification (ASJC) codes

General

Keywords

Actin
Dendritic spines
Protein phosphatase

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10.1073/pnas.0409802102

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title = "Phosphorylation of spinophilin by ERK and cyclin-dependent PK 5 (Cdk5)",

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.",

keywords = "Actin, Dendritic spines, Protein phosphatase",

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T1 - Phosphorylation of spinophilin by ERK and cyclin-dependent PK 5 (Cdk5)

AU - Futter, Marie

AU - Uematsu, Ken

AU - Bullock, Stewart A.

AU - Kim, Yong

AU - Hemmings, Hugh C.

AU - Nishi, Akinori

AU - Greengard, Paul

AU - Nairn, Angus C.

PY - 2005/3/1

Y1 - 2005/3/1

N2 - 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.

AB - 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.

KW - Actin

KW - Dendritic spines

KW - Protein phosphatase

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JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 9

ER -

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

Abstract

All Science Journal Classification (ASJC) codes

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