title: Tyrosine kinase 2 interacts with and phosphorylates receptor for activated C kinase-1, a WD motif-containing protein.
abstract: Receptor for activated C kinase (Rack)-1 is a protein kinase C-interacting protein, and contains a WD repeat but has no enzymatic activity. In addition to protein kinase C, Rack-1 also binds to Src, phospholipase Cgamma, and ras-GTPase-activating proteins. Thus, Rack-1 is thought to function as a scaffold protein that recruits specific signaling elements. In a cytokine signaling cascade, Rack-1 has been reported to interact with the IFN-alphabeta receptor and Stat1. In addition, we show here that Rack-1 associates with a member of Jak, tyrosine kinase 2 (Tyk2). Rack-1 interacts weakly with the kinase domain and interacts strongly with the pseudokinase domain of Tyk2. Rack-1 associates with Tyk2 via two regions, one in the N terminus and one in the middle portion (aa 138-203) of Rack-1. Jak activation causes the phosphorylation of tyrosine 194 on Rack-1. After phosphorylation, Rack-1 is translocated toward the perinuclear region. In addition to functioning as a scaffolding protein, these results raise the possibility that Rack-1 functions as a signaling molecule in cytokine signaling cascades.
authors.affiliation: First Department of Internal Medicine, Faculty of Medicine, and Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Haro
authors.forename: Kazuya
authors.initials: K
authors.lastname: Shimoda
authors.forename: Haruko
authors.initials: H
authors.lastname: Kakumitsu
authors.forename: Kenjirou
authors.initials: K
authors.lastname: Kamezaki
authors.forename: Akihiko
authors.initials: A
authors.lastname: Numata
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Ishikawa
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sekine
authors.forename: Ryuta
authors.initials: R
authors.lastname: Muromoto
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsuda
authors.forename: Mine
authors.initials: M
authors.lastname: Harada
mesh_terms: D020816:Amino Acid Motifs; D006801:Humans; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000378:metabolism*; D053634:TYK2 Kinase; D014443:Tyrosine / Q000378:metabolism
chemical_list: D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D053634:TYK2 Kinase; C070139:TYK2 protein, human