Universität zu Köln

Araki, Tsuyoshi, Sasaki, Norimitsu, Kawata, Takefumi ORCID: 0000-0002-3685-4492, Eichinger, Ludwig ORCID: 0000-0003-1594-6117 and Williams, Jeffrey G. (2014). Two Dictyostelium tyrosine kinase-like kinases function in parallel, stress-induced STAT activation pathways. Mol. Biol. Cell, 25 (20). S. 3222 - 3234. BETHESDA: AMER SOC CELL BIOLOGY. ISSN 1939-4586

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Abstract

When Dictyostelium cells are hyperosmotically 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 stress-induced STATc activation, single null mutants are only marginally impaired, but the double mutant is nonactivatable. When cells are stressed, Pyk2 and Pyk3 undergo increased autocatalytic 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 signaling 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 catalyze 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, whereas Pyk2 accumulates in cytosolic granules that colocalize with PTP3.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Araki, Tsuyoshi UNSPECIFIED UNSPECIFIED UNSPECIFIED Sasaki, Norimitsu UNSPECIFIED UNSPECIFIED UNSPECIFIED Kawata, Takefumi UNSPECIFIED orcid.org/0000-0002-3685-4492 UNSPECIFIED Eichinger, Ludwig UNSPECIFIED orcid.org/0000-0003-1594-6117 UNSPECIFIED Williams, Jeffrey G. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-425742
DOI:	10.1091/mbc.E14-07-1182
Journal or Publication Title:	Mol. Biol. Cell
Volume:	25
Number:	20
Page Range:	S. 3222 - 3234
Date:	2014
Publisher:	AMER SOC CELL BIOLOGY
Place of Publication:	BETHESDA
ISSN:	1939-4586
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PSEUDOKINASE DOMAIN; SIGNALING PATHWAY; MYOSIN PHOSPHORYLATION; PROTEIN-KINASE; OSMOTIC SHOCK; CGMP; DISCOIDEUM; JAK2; IDENTIFICATION; ACCUMULATION Multiple languages Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/42574