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PMID:16982696

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Citation

Yang, YC, Lin, CH and Lee, EH (2006) Serum- and glucocorticoid-inducible kinase 1 (SGK1) increases neurite formation through microtubule depolymerization by SGK1 and by SGK1 phosphorylation of tau. Mol. Cell. Biol. 26:8357-70

Abstract

Serum- and glucocorticoid-inducible kinase 1 (SGK1) is a member of the Ser/Thr protein kinase family that regulates a variety of cell functions. Recently, SGK1 was shown to increase dendritic growth but the mechanism underlying the increase is unknown. Here we demonstrated that SGK1 increased the neurite formation of cultured hippocampal neurons through microtubule (MT) depolymerization via two distinct mechanisms. First, SGK1 directly depolymerized MTs. In vitro MT depolymerization experiments revealed that SGK1, especially N-truncated SGK1, directly disassembled self-polymerized MTs and taxol-stabilized MTs in a dose-dependent and ATP-independent manner. The transfection of sgk1 to HeLa cells also inhibited MT assembly in vivo. Second, SGK1 indirectly depolymerized MTs through the phosphorylation of tau at Ser214. An in vitro kinase assay revealed that active SGK1 phosphorylated tau Ser214 specifically. In vivo transfection of sgk1 also phosphorylated tau Ser214 in HEK293T cells and hippocampal neurons. Further, sgk1 transfection significantly increased the number of primary neurites and shortened the length of the total process in cultured hippocampal neurons. These effects were antagonized by the cotransfection of the tauS214A mutant plasmid. Dexamethasone, a synthetic glucocorticoid, mimics the effect of sgk1 overexpression. Together, these results suggest that SGK1 enhances neurite formation through MT depolymerization by a direct action of SGK1 and by the SGK1 phosphorylation of tau.

Links

PubMed PMC1636775 Online version:10.1128/MCB.01017-06

Keywords

Animals; Cells, Cultured; Female; Hippocampus/cytology; Hippocampus/enzymology; Immediate-Early Proteins/genetics; Immediate-Early Proteins/metabolism; Immediate-Early Proteins/physiology; Microtubules/physiology; Neurites/enzymology; Neurites/physiology; Neurons/enzymology; Neurons/physiology; Phosphorylation; Protein-Serine-Threonine Kinases/genetics; Protein-Serine-Threonine Kinases/metabolism; Protein-Serine-Threonine Kinases/physiology; Rats; Rats, Sprague-Dawley; Serine; Transfection; tau Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:SGK1

involved_in

GO:0031115: negative regulation of microtubule polymerization

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:SGK1

involved_in

GO:0007019: microtubule depolymerization

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:SGK1

enables

GO:0004674: protein serine/threonine kinase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:SGK1

located_in

GO:0043005: neuron projection

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:SGK1

enables

GO:0048156: tau protein binding

ECO:0000353: physical interaction evidence used in manual assertion

RGD:69329

F

Seeded From UniProt

complete

RAT:SGK1

involved_in

GO:0018105: peptidyl-serine phosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:SGK1

involved_in

GO:0043402: glucocorticoid mediated signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:SGK1

involved_in

GO:0048812: neuron projection morphogenesis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:TAU

enables

GO:0019901: protein kinase binding

ECO:0000353: physical interaction evidence used in manual assertion

RGD:3668

F

Seeded From UniProt

complete


See also

References

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