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.
authors.affiliation: Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10021, USA.
authors.forename: Marie
authors.initials: M
authors.lastname: Futter
authors.forename: Ken
authors.initials: K
authors.lastname: Uematsu
authors.forename: Stewart A
authors.initials: SA
authors.lastname: Bullock
authors.forename: Yong
authors.initials: Y
authors.lastname: Kim
authors.forename: Hugh C
authors.initials: HC
authors.lastname: Hemmings
authors.forename: Akinori
authors.initials: A
authors.lastname: Nishi
authors.forename: Paul
authors.initials: P
authors.lastname: Greengard
authors.forename: Angus C
authors.initials: AC
authors.lastname: Nairn
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D009024:Morphogenesis; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D010449:Peptide Mapping; D010766:Phosphorylation; D011485:Protein Binding; D000099273:Neurabins
chemical_list: D000199:Actins; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases; D008840:Microfilament Proteins; D019950:Mitogen-Activated Protein Kinase 1; D009419:Nerve Tissue Proteins; D000099273:Neurabins; C495905:CDK5 protein, human; C495906:Cdk5 protein, mouse
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