Tyrosine kinase 2 interacts with and phosphorylates receptor for activated C kinase-1, a WD motif-containing protein.
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.
Haro
Takashi
T
First Department of Internal Medicine, Faculty of Medicine, and Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Shimoda
Kazuya
K
Kakumitsu
Haruko
H
Kamezaki
Kenjirou
K
Numata
Akihiko
A
Ishikawa
Fumihiko
F
Sekine
Yuichi
Y
Muromoto
Ryuta
R
Matsuda
Tadashi
T
Harada
Mine
M
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
D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D053634:TYK2 Kinase; C070139:TYK2 protein, human