title: Protein kinase CK2 enhances Mcl-1 gene expression through the serum response factor-mediated pathway in the rat hippocampus.
abstract: The protein kinase CK2 (casein kinase 2) is a ubiquitous serine/threonine protein kinase that suppresses apoptosis. CK2 is composed of catalytic and regulatory subunits, and CK2-dependent phosphorylation is a global mechanism in the inhibition of caspase signaling pathways. The serum response factor (SRF) is an important regulator of cell growth and differentiation. Although CK2 has been shown to phosphorylate SRF in vitro, the biological relevance of this interaction remains largely unclear. We observed increased SRF phosphorylation and increased Mcl-1 gene expression in hippocampal CA1 neurons following transfection with a plasmid expressing the wild-type CK2α (CK2αWT) protein, whereas transfection with a plasmid expressing a catalytically inactive mutant of CK2α (CK2α156A) reduced Mcl-1 gene expression. Cotransfection with a plasmid expressing the inactive SRF99A mutant inhibited the CK2αWT-induced upregulation of Mcl-1 gene expression. The expression of either the CK2α156A or the SRF99A mutant also inhibited the glutamate-induced upregulation of Mcl-1 protein expression in PC12 cells. Our results suggest that CK2-mediated signaling represents a cellular mechanism that may aid in the development of alternative therapeutic strategies to attenuate apoptosis in hippocampal neurons.
authors.affiliation: Institute of Neurosciences, National Chengchi University, Taipei, Taiwan.
authors.forename: Chia-Ming
authors.initials: CM
authors.lastname: Chang
authors.forename: Chih Chang
authors.initials: CC
authors.lastname: Chao
mesh_terms: D000818:Animals; D047390:Casein Kinase II / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism*; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008297:Male; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D016716:PC12 Cells; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D026362:Serum Response Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection
chemical_list: D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D026362:Serum Response Factor; D047390:Casein Kinase II