Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.5.1.18 (
glutathione S-transferase
)
22,582
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Cyclin-dependent kinase 5 (Cdk5) is predominantly expressed in the nervous system, where it is involved in neuronal migration, synaptic transmission, and survival. The role of Cdk5 in synaptic transmission is mediated by regulating the cellular functions of presynaptic proteins such as synapsin, Munc18, and dynamin 1. Its multifunctional role at the synapse is complex and probably involves other novel substrates. To explore this possibility, we used a yeast two-hybrid screen of a human cDNA library with p35 as bait and isolated human
septin 5
(
SEPT5
), known also as hCDCrel-1, as an interacting clone. Here we report that p35 associates with
SEPT5
in
GST
(
glutathione S-transferase
)-pull-down and coimmunoprecipitation assays. We confirmed that Cdk5/p35 phosphorylates
SEPT5
in vitro and in vivo and identified S327 of
SEPT5
as a major phosphorylation site. A serine (S)-to-alanine (A) 327 mutant of
SEPT5
bound syntaxin more efficiently than
SEPT5
wild type. Additionally, coimmunoprecipitation from synaptic vesicle fractions and Cdk5 wild-type and knock-out lysates showed that phosphorylation of
septin 5
by Cdk5/p35 decreases its binding to syntaxin-1. Moreover, mutant nonphosphorylated
SEPT5
potentiated regulated exocytosis more than the wild type when each was expressed in PC12 cells. These data suggest that Cdk5 phosphorylation of human septin
SEPT5
at S327 plays a role in modulating exocytotic secretion.
...
PMID:Cyclin-dependent kinase 5 phosphorylation of human septin SEPT5 (hCDCrel-1) modulates exocytosis. 1838 22
