title: Casein kinase 2 interacts with human mitogen- and stress-activated protein kinase MSK1 and phosphorylates it at multiple sites.
abstract: Mitogen- and stress-activated protein kinase (MSK1) palys a crucial role in the regulation of transcription downstream of extracellular-signal-regulated kinase1/2 (ERK1/2) and mitogen- activated protein kinase p38. MSK1 can be phosphorylated and activated in cells by both ERK1/2 and p38alpha. In this study, Casein Kinase 2 (CK2) was identified as a binding and regulatory partner for MSK1. Using the yeast two-hybrid system, MSK1 was found to interact with the CK2beta regulatory subunit of CK2. Interactions between MSK1 and the CK2alpha catalytic subunit and CK2beta subunit were demonstrated in vitro and in vivo. We further found that CK2alpha can only interact with the C-terminal kinase domain of MSK1. Using site-directed mutagenesis assay and mass spectrometry, we identified five sites in the MSK1 C-terminus that could be phosphorylated by CK2 in vitro: Ser757, Ser758, Ser759, Ser760 and Thr793. Of these, Ser757, Ser759, Ser760 and Thr793 were previously unknown.
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, 220 Handan Rd, Shanghai 200433, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Shi
authors.forename: Guanghui
authors.initials: G
authors.lastname: Han
authors.forename: Huiling
authors.initials: H
authors.lastname: Wu
authors.forename: Kan
authors.initials: K
authors.lastname: Ye
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Tian
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Wang
authors.forename: Huili
authors.initials: H
authors.lastname: Shi
authors.forename: Mingliang
authors.initials: M
authors.lastname: Ye
authors.forename: Hanfa
authors.initials: H
authors.lastname: Zou
authors.forename: Keke
authors.initials: K
authors.lastname: Huo
mesh_terms: D001665:Binding Sites; D047390:Casein Kinase II / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D011485:Protein Binding; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000737:chemistry / Q000378:metabolism*
chemical_list: D047390:Casein Kinase II; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C116919:mitogen and stress-activated protein kinase 1