| FAFÍLEK, Bohumil, Lukáš BÁLEK, Michaela BOSÁKOVÁ, Miroslav VAŘECHA, Alexandru NITĂ, Tomáš GREGOR, Iva GUDERNOVÁ, Jitka KŘENOVÁ, S. GHOSH, Martin PISKÁČEK, Lucie JONATOVA, Nicole ČERNOHORSKÁ, J.T. ZIEBA, M. KOSTAS, E.M. HAUGSTEN, J. WESCHE, C. ERNEUX, Lukáš TRANTÍREK, D. KRAKOW and Pavel KREJČÍ. The inositol phosphatase SHIP2 enables sustained ERK activation downstream of FGF receptors by recruiting Src kinases. SCIENCE SIGNALING. WASHINGTON: AMER ASSOC ADVANCEMENT SCIENCE, vol. 11, No 548, p. 1-14. ISSN 1945-0877. doi:10.1126/scisignal.aap8608. 2018. |
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@article{1490481,
author = {Fafílek, Bohumil and Bálek, Lukáš and Bosáková, Michaela and Vařecha, Miroslav and Nită, Alexandru and Gregor, Tomáš and Gudernová, Iva and Křenová, Jitka and Ghosh, S. and Piskáček, Martin and Jonatova, Lucie and Černohorská, Nicole and Zieba, J.T. and Kostas, M. and Haugsten, E.M. and Wesche, J. and Erneux, C. and Trantírek, Lukáš and Krakow, D. and Krejčí, Pavel},
article_location = {WASHINGTON},
article_number = {548},
doi = {http://dx.doi.org/10.1126/scisignal.aap8608},
keywords = {The inositol phosphatase SHIP2},
language = {eng},
issn = {1945-0877},
journal = {SCIENCE SIGNALING},
title = {The inositol phosphatase SHIP2 enables sustained ERK activation downstream of FGF receptors by recruiting Src kinases},
volume = {11},
year = {2018}
}
TY - JOUR
ID - 1490481
AU - Fafílek, Bohumil - Bálek, Lukáš - Bosáková, Michaela - Vařecha, Miroslav - Nită, Alexandru - Gregor, Tomáš - Gudernová, Iva - Křenová, Jitka - Ghosh, S. - Piskáček, Martin - Jonatova, Lucie - Černohorská, Nicole - Zieba, J.T. - Kostas, M. - Haugsten, E.M. - Wesche, J. - Erneux, C. - Trantírek, Lukáš - Krakow, D. - Krejčí, Pavel
PY - 2018
TI - The inositol phosphatase SHIP2 enables sustained ERK activation downstream of FGF receptors by recruiting Src kinases
JF - SCIENCE SIGNALING
VL - 11
IS - 548
SP - 1-14
EP - 1-14
PB - AMER ASSOC ADVANCEMENT SCIENCE
SN - 19450877
KW - The inositol phosphatase SHIP2
N2 - 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.
ER -
FAFÍLEK, Bohumil, Lukáš BÁLEK, Michaela BOSÁKOVÁ, Miroslav VAŘECHA, Alexandru NIT$\backslash$U A, Tomáš GREGOR, Iva GUDERNOVÁ, Jitka KŘENOVÁ, S. GHOSH, Martin PISKÁČEK, Lucie JONATOVA, Nicole ČERNOHORSKÁ, J.T. ZIEBA, M. KOSTAS, E.M. HAUGSTEN, J. WESCHE, C. ERNEUX, Lukáš TRANTÍREK, D. KRAKOW and Pavel KREJČÍ. The inositol phosphatase SHIP2 enables sustained ERK activation downstream of FGF receptors by recruiting Src kinases. \textit{SCIENCE SIGNALING}. WASHINGTON: AMER ASSOC ADVANCEMENT SCIENCE, vol.~11, No~548, p.~1-14. ISSN~1945-0877. doi:10.1126/scisignal.aap8608. 2018.
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