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:2.7.13.3 (
histidine kinase
)
2,405
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
We report localization of a cytosolic protein histidine phosphatase (
PHP
; approximately 16 kDa) in INS 832/13 cells, normal rat islets, and human islets. siRNA-mediated knockdown of
PHP
markedly reduced glucose- or mitochondrial fuel-induced but not KCl-induced insulin secretion. siRNA-mediated knockdown of
PHP
also attenuated mastoparan-induced insulin secretion, suggesting its participation in G protein-sensitive signaling steps, leading to insulin secretion. Functional assays revealed that the beta-cell
PHP
catalyzes the dephosphorylation of ATP-citrate lyase (ACL). Silencing of
PHP
expression markedly reduced ACL activity, suggesting functional regulation of ACL by
PHP
in beta-cells. Coimmunoprecipitation studies revealed modest effects of glucose on the interaction between
PHP
and ACL. Confocal microscopic evidence indicated that glucose promotes association between ACL and nm23-H1, a known kinase
histidine kinase
, but not between
PHP
and ACL. Furthermore, metabolic viability of INS 832/13 cells was resistant to siRNA-
PHP
, suggesting no regulatory roles of
PHP
in cell viability. Finally, long-term exposure (24 h) of INS 832/13 cells or rat islets to high glucose (30 mM) increased the expression of
PHP
. Such increases in
PHP
expression were also seen in islets derived from the Zucker diabetic fatty rat compared with islets from the lean control animals. Together, these data implicate regulatory roles for
PHP
in a G protein-sensitive step involved in nutrient-induced insulin secretion. In light of the current debate on putative regulatory roles of ACL in insulin secretion, additional studies are needed to precisely identify the phosphoprotein substrate(s) for
PHP
in the cascade of events leading to nutrient-induced insulin secretion.
...
PMID:Regulation of glucose- and mitochondrial fuel-induced insulin secretion by a cytosolic protein histidine phosphatase in pancreatic beta-cells. 2050 72
