カワタ　タケフミ   Kawata Takefumi   川田　健文    所属   東邦大学  理学部 生物学科    職種   教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Two Dictyostelium Tyrosine Kinase-Like kinases function in parallel, stress-induced STAT activation pathways
掲載誌名	正式名：Molecular Biology of the Cell ISSNコード：1059-1524
出版社	AMER SOC CELL BIOLOGY
巻・号・頁	25,pp.3222-3233
著者・共著者	Araki T, Vu LH, Sasaki N†, Kawata T†, Eichinger L, Williams JG
発行年月	2014/09
概要	When Dictyostelium cells are hyper-osmotically stressed STATc is activated by tyrosine phosphorylation. Unusually, activation is regulated by serine phosphorylation and consequent inhibition of a tyrosine phosphatase: PTP3. The identity of the cognate tyrosine kinase is unknown and we show that two Tyrosine Kinase-Like (TKL) enzymes, Pyk2 and Pyk3, share this function; thus for stressinduced STATc activation, single null mutants are only marginally impaired but the double mutant is non-activatable. When cells are stressed Pyk2 and Pyk3 undergo increased auto-catalytic tyrosine phosphorylation. The site(s) that are generated bind the SH2 domain of STATc and then STATc becomes the target of further kinase action. The signalling pathways that activate Pyk2 and Pyk3 are only partially overlapping and there may be a structural basis for this difference because Pyk3 contains both a TKL domain and a pseudokinase domain. The latter functions, like the JH2 domain of metazoan JAKs, as a negative regulator of the kinase domain. The fact that two differently regulated kinases catalyse the same phosphorylation event may facilitate specific targeting because under stress Pyk3 and Pyk2 accumulate in different parts of the cell; Pyk3 moves from the cytosol to the cortex while Pyk2 accumulates in cytosolic granules that co-localise with PTP3.
DOI	10.1091/mbc.E14-04-0917