Biochemical and Biophysical Research Communications, Vol.471, No.1, 205-212, 2016
Cobalt chloride-mediated protein kinase C alpha (PKC alpha) phosphorylation induces hypoxia-inducible factor 1 alpha (HIF1 alpha) in the nucleus of gastric cancer cell
Hypoxia promotes cancer progression, and metastasis. The major protein expressed in hypoxic solid cancer is hypoxia-inducible factor 1 (HIF1). We show that enhanced phosphorylation of a conventional protein kinase C isoform, PKC alpha, at threonine 638 (T-638) by hypoxia-mimetic cobalt chloride induces HIF1 alpha in nuclei of gastric epithelial cells (GECs). Moreover, phospho-T-638-PKC alpha (P-PKC alpha) interacts with p300-HIF1 alpha complex in the nuclei of hypoxic GECs and PKC alpha phosphorylation at T-638 enhances transcriptional activity of HIF1 alpha. High P-PKC alpha expression in neoplastic gastric cancer biopsy samples as compared to nonneoplastic samples suggests that P-PKC alpha might act as an indicator of gastric cancer progression. (C) 2016 Elsevier Inc. All rights reserved.