Proteomic analyses of signalling complexes associated with
receptor tyrosine kinase identify novel members of fibroblast
growth factor receptor 3 interactome

J 2018

Proteomic analyses of signalling complexes associated with receptor tyrosine kinase identify novel members of fibroblast growth factor receptor 3 interactome

BÁLEK, Lukáš, Pavel NĚMEC, P. KONIK, Michaela BOSÁKOVÁ, Miroslav VAŘECHA et. al.

Basic information

Original name

Proteomic analyses of signalling complexes associated with receptor tyrosine kinase identify novel members of fibroblast growth factor receptor 3 interactome

Authors

BÁLEK, Lukáš (203 Czech Republic, belonging to the institution), Pavel NĚMEC (203 Czech Republic, belonging to the institution), P. KONIK (203 Czech Republic), Michaela BOSÁKOVÁ (203 Czech Republic, belonging to the institution), Miroslav VAŘECHA (203 Czech Republic, belonging to the institution), Iva GUDERNOVÁ (203 Czech Republic, belonging to the institution), Jiřina MEDALOVÁ (203 Czech Republic, belonging to the institution), Deborah KRAKOW (840 United States of America) and Pavel KREJČÍ (203 Czech Republic, guarantor, belonging to the institution)

Edition

Cellular Signalling, New York, Elsevier Science, 2018, 0898-6568

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10601 Cell biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 3.388

RIV identification code

RIV/00216224:14110/18:00100747

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1016/j.cellsig.2017.10.003

UT WoS

000423893200015

Keywords in English

FGFR3; Fibroblast growth factor; interactome; receptor tyrosine kinase; signal transduction

Abstract

V originále

Receptor tyrosine kinases (RTKs) form multiprotein complexes that initiate and propagate intracellular signals and determine the RTK-specific signalling patterns. Unravelling the full complexity of protein interactions within the RTK-associated complexes is essential for understanding of RTK functions, yet it remains an understudied area of cell biology. We describe a comprehensive approach to characterize RTK interactome. A single tag immunoprecipitation and phosphotyrosine protein isolation followed by mass-spectrometry was used to identify proteins interacting with fibroblast growth factor receptor 3 (FGFR3). A total of 32 experiments were carried out in two different cell types and identified 66 proteins out of which only 20 (30.3%) proteins were already known FGFR interactors. Using co-immunoprecipitations, we validated FGFR3 interaction with adapter protein STAM1, transcriptional regulator SHOX2, translation elongation factor eEF1A1, serine/threonine kinases ICK, MAK and CCRK, and inositol phosphatase SHIP2. We show that unappreciated signalling mediators exist for well-studied RTKs, such as FGFR3, and may be identified via proteomic approaches described here. These approaches are easily adaptable to other RTKs, enabling identification of novel signalling mediators for majority of the known human RTKs.

Links

GA17-09525S, research and development project

Name: Neobvyklé signální dráhy lidských receptorových tyrozinových kináz

Investor: Czech Science Foundation

LH15231, research and development project

Name: Nové mechanismy vzniku fatálních kostních ciliopatií u člověka

Investor: Ministry of Education, Youth and Sports of the CR

NV15-33232A, research and development project

Name: Identifikace nových možností léčby achondroplásie prostřednictvím analýzy interakce FGFR3 a adaptérového proteinu Frs2

NV15-34405A, research and development project

Name: Identifikace nových možností léčby chronické myeloidní leukémie pomocí systematické analýzy interaktomu proteinu BCR-ABL

ROZV/24/LF/2016, interní kód MU

Name: LF - Příspěvek IP 2016

Investor: Ministry of Education, Youth and Sports of the CR

Citovat

BÁLEK, Lukáš, Pavel NĚMEC, P. KONIK, Michaela BOSÁKOVÁ, Miroslav VAŘECHA, Iva GUDERNOVÁ, Jiřina MEDALOVÁ, Deborah KRAKOW and Pavel KREJČÍ. Proteomic analyses of signalling complexes associated with receptor tyrosine kinase identify novel members of fibroblast growth factor receptor 3 interactome. Cellular Signalling. New York: Elsevier Science, 2018, vol. 42, JAN 2018, p. 144-154. ISSN 0898-6568. Available from: https://dx.doi.org/10.1016/j.cellsig.2017.10.003.

@article{1395567,
   author = {Bálek, Lukáš and Němec, Pavel and Konik, P. and Bosáková, Michaela and Vařecha, Miroslav and Gudernová, Iva and Medalová, Jiřina and Krakow, Deborah and Krejčí, Pavel},
   article_location = {New York},
   article_number = {JAN 2018},
   doi = {http://dx.doi.org/10.1016/j.cellsig.2017.10.003},
   keywords = {FGFR3; Fibroblast growth factor; interactome; receptor tyrosine kinase; signal transduction},
   language = {eng},
   issn = {0898-6568},
   journal = {Cellular Signalling},
   title = {Proteomic analyses of signalling complexes associated with receptor tyrosine kinase identify novel members of fibroblast growth factor receptor 3 interactome},
   volume = {42},
   year = {2018}
}

TY  - JOUR
ID  - 1395567
AU  - Bálek, Lukáš - Němec, Pavel - Konik, P. - Bosáková, Michaela - Vařecha, Miroslav - Gudernová, Iva - Medalová, Jiřina - Krakow, Deborah - Krejčí, Pavel
PY  - 2018
TI  - Proteomic analyses of signalling complexes associated with receptor tyrosine kinase identify novel members of fibroblast growth factor receptor 3 interactome
JF  - Cellular Signalling
VL  - 42
IS  - JAN 2018
SP  - 144-154
EP  - 144-154
PB  - Elsevier Science
SN  - 08986568
KW  - FGFR3
KW  - Fibroblast growth factor
KW  - interactome
KW  - receptor tyrosine kinase
KW  - signal transduction
N2  - Receptor tyrosine kinases (RTKs) form multiprotein complexes that initiate and propagate intracellular signals and determine the RTK-specific signalling patterns. Unravelling the full complexity of protein interactions within the RTK-associated complexes is essential for understanding of RTK functions, yet it remains an understudied area of cell biology. We describe a comprehensive approach to characterize RTK interactome. A single tag immunoprecipitation and phosphotyrosine protein isolation followed by mass-spectrometry was used to identify proteins interacting with fibroblast growth factor receptor 3 (FGFR3). A total of 32 experiments were carried out in two different cell types and identified 66 proteins out of which only 20 (30.3%) proteins were already known FGFR interactors. Using co-immunoprecipitations, we validated FGFR3 interaction with adapter protein STAM1, transcriptional regulator SHOX2, translation elongation factor eEF1A1, serine/threonine kinases ICK, MAK and CCRK, and inositol phosphatase SHIP2. We show that unappreciated signalling mediators exist for well-studied RTKs, such as FGFR3, and may be identified via proteomic approaches described here. These approaches are easily adaptable to other RTKs, enabling identification of novel signalling mediators for majority of the known human RTKs.
ER  -

BÁLEK, Lukáš, Pavel NĚMEC, P. KONIK, Michaela BOSÁKOVÁ, Miroslav VAŘECHA, Iva GUDERNOVÁ, Jiřina MEDALOVÁ, Deborah KRAKOW and Pavel KREJČÍ. Proteomic analyses of signalling complexes associated with receptor tyrosine kinase identify novel members of fibroblast growth factor receptor 3 interactome. \textit{Cellular Signalling}. New York: Elsevier Science, 2018, vol.~42, JAN 2018, p.~144-154. ISSN~0898-6568. Available from: https://dx.doi.org/10.1016/j.cellsig.2017.10.003.

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