Detailed Information on Publication Record
2018
The inositol phosphatase SHIP2 enables sustained ERK activation downstream of FGF receptors by recruiting Src kinases
FAFÍLEK, Bohumil, Lukáš BÁLEK, Michaela BOSÁKOVÁ, Miroslav VAŘECHA, Alexandru NITĂ et. al.Basic information
Original name
The inositol phosphatase SHIP2 enables sustained ERK activation downstream of FGF receptors by recruiting Src kinases
Authors
FAFÍLEK, Bohumil (203 Czech Republic, belonging to the institution), Lukáš BÁLEK (203 Czech Republic, belonging to the institution), Michaela BOSÁKOVÁ (203 Czech Republic, belonging to the institution), Miroslav VAŘECHA (203 Czech Republic, belonging to the institution), Alexandru NITĂ (642 Romania, belonging to the institution), Tomáš GREGOR (203 Czech Republic, belonging to the institution), Iva GUDERNOVÁ (203 Czech Republic, belonging to the institution), Jitka KŘENOVÁ (203 Czech Republic, belonging to the institution), S. GHOSH (56 Belgium), Martin PISKÁČEK (40 Austria, belonging to the institution), Lucie JONATOVA (203 Czech Republic), Nicole ČERNOHORSKÁ (203 Czech Republic, belonging to the institution), J.T. ZIEBA (840 United States of America), M. KOSTAS (578 Norway), E.M. HAUGSTEN (578 Norway), J. WESCHE (578 Norway), C. ERNEUX (56 Belgium), Lukáš TRANTÍREK (203 Czech Republic, belonging to the institution), D. KRAKOW (840 United States of America) and Pavel KREJČÍ (203 Czech Republic, guarantor, belonging to the institution)
Edition
SCIENCE SIGNALING, WASHINGTON, AMER ASSOC ADVANCEMENT SCIENCE, 2018, 1945-0877
Other information
Language
English
Type of outcome
Článek v odborném periodiku
Field of Study
10608 Biochemistry and molecular biology
Country of publisher
United States of America
Confidentiality degree
není předmětem státního či obchodního tajemství
Impact factor
Impact factor: 6.565
RIV identification code
RIV/00216224:14110/18:00101653
Organization unit
Faculty of Medicine
UT WoS
000444825300002
Keywords in English
The inositol phosphatase SHIP2
Tags
International impact, Reviewed
Změněno: 8/3/2019 16:00, Mgr. Pavla Foltynová, Ph.D.
Abstract
V originále
Sustained activation of extracellular signal-regulated kinase (ERK) drives pathologies caused by mutations in fibroblast growth factor receptors (FGFRs). We previously identified the inositol phosphatase SHIP2 (also known as INPPL1) as an FGFR-interacting protein and a target of the tyrosine kinase activities of FGFR1, FGFR3, and FGFR4. We report that loss of SHIP2 converted FGF-mediated sustained ERK activation into a transient signal and rescued cell phenotypes triggered by pathologic FGFR-ERK signaling. Mutant forms of SHIP2 lacking phosphoinositide phosphatase activity still associated with FGFRs and did not prevent FGF-induced sustained ERK activation, demonstrating that the adaptor rather than the catalytic activity of SHIP2 was required. SHIP2 recruited Src family kinases to the FGFRs, which promoted FGFR-mediated phosphorylation and assembly of protein complexes that relayed signaling to ERK. SHIP2 interacted with FGFRs, was phosphorylated by active FGFRs, and promoted FGFR-ERK signaling at the level of phosphorylation of the adaptor FRS2 and recruitment of the tyrosine phosphatase PTPN11. Thus, SHIP2 is an essential component of canonical FGF-FGFR signal transduction and a potential therapeutic target in FGFR-related disorders.
Links
| GA17-09525S, research and development project |
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| LH15231, research and development project |
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| LQ1601, research and development project |
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| NV15-33232A, research and development project |
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| NV15-34405A, research and development project |
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| ROZV/25/LF/2017, interní kód MU |
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