Arsenic-Induced Activation of the Homeodomain-Interacting Protein Kinase 2 (HIPK2) to cAMP-Response Element Binding Protein (CREB) Axis.

ABSTRACT: Cyclic AMP-response element-binding protein (CREB) plays key transcriptional roles in cell metabolism, proliferation, and survival. Ser133 phosphorylation by protein kinase A (PKA) is a well-characterized CREB activation mechanism. Homeodomain-interacting protein kinase (HIPK) 2, a nuclear serine/threonine kinase, activates CREB through Ser271 phosphorylation; however, the regulatory mechanism remains uncharacterized. Transfection of CREB in HEK293 cells together with the kinase demonstrated that HIPK2 phosphorylated CREB at Ser271 but not Ser133; likewise, PKA phosphorylated CREB at Ser133 but not Ser271, suggesting two distinct CREB regulatory mechanisms by HIPK2 and PKA. In vitro kinase assay revealed that HIPK2, and HIPK1 and HIPK3, directly phosphorylated CREB. Cells exposed to 10μM s

SUBMITTER: Hashimoto K 

PROVIDER: S-EPMC5186405 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature