J 2011

Post-translational modifications regulate signalling by Ror1

KAUCKÁ, Markéta, Pavel KREJČÍ, Karla PLEVOVÁ, Šárka PAVLOVÁ, Jiřina PROCHÁZKOVÁ et. al.

Basic information

Original name

Post-translational modifications regulate signalling by Ror1

Authors

KAUCKÁ, Markéta (203 Czech Republic, belonging to the institution), Pavel KREJČÍ (203 Czech Republic, belonging to the institution), Karla PLEVOVÁ (203 Czech Republic, belonging to the institution), Šárka PAVLOVÁ (203 Czech Republic, belonging to the institution), Jiřina PROCHÁZKOVÁ (203 Czech Republic, belonging to the institution), Pavlína JANOVSKÁ (203 Czech Republic, belonging to the institution), Jana VALNOHOVÁ (203 Czech Republic, belonging to the institution), Alois KOZUBÍK (203 Czech Republic, belonging to the institution), Šárka POSPÍŠILOVÁ (203 Czech Republic, belonging to the institution) and Vítězslav BRYJA (203 Czech Republic, guarantor)

Edition

Acta Physiologica, Oxford, Blackwell Publishing, 2011, 1748-1708

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

Genetics and molecular biology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 3.090

RIV identification code

RIV/00216224:14310/11:00050218

Organization unit

Faculty of Science

DOI

UT WoS

000296061800002

Keywords in English

Ror1; posttranslational modifications; glycosylation; chronic lymphocytic leukemia

Tags

Změněno: 20/4/2012 11:39, Ing. Andrea Mikešková

Abstract

V originále

Ror1 (receptor tyrosine kinase-like orphan receptor)is highly upregulated in B cells of patients with chronic lymphocytic leukaemia (CLL). Ror1 acts as the Wnt receptor in the non-canonical Wnt pathway. We demonstrate that Ror1 is extensively modified by N-linked glycosylation. Glycosylation produces several variants of Ror1 with electrophoretic migration of approx. 100, 115 and 130 kDa. Inhibition of glycosylation interferes with cell surface localization of the 130-kDa variant of Ror1 and prevents Ror1-induced formation of filopodia. Moreover, we show that 130-kDa Ror1 is mono-ubiquitinated. Furthermore, individual CLL patients show striking differences in the electrophoretic migration of Ror1, which correspond to the level of glycosylation. Our data show that Ror1 undergoes complex post-translational modifications by glycosylation and mono-ubiquitination. These modifications regulate Ror1 localization and signalling, and are highly variable among individual CLL patients. These may suggest that Ror1 signals only in a subset of CLL patients despite Ror1 levels are ubiquitously high in all CLL patients.

Links

GAP301/11/0747, research and development project
Name: Molekulární mechanismy nekanonické Wnt signalizace v leukémii
Investor: Czech Science Foundation
GAP305/11/0752, research and development project
Name: Molekulární základy FGFR3 signalingu v kostní dysplázii
Investor: Czech Science Foundation
GA301/09/0587, research and development project
Name: Nové dráhy FGFR3 signalingu v achondroplázii
Investor: Czech Science Foundation, Novel pathway of FGFR3 signaling in achondroplasia
GD204/09/H058, research and development project
Name: Mezibuněčná signalizace ve vývoji organismu a vzniku onemocnění
Investor: Czech Science Foundation, Intercellular signalling in development and disease
MSM0021622430, plan (intention)
Name: Funkční a molekulární charakteristiky nádorových a normálních kmenových buněk - identifikace cílů pro nová terapeutika a terapeutické strategie
Investor: Ministry of Education, Youth and Sports of the CR, Functional and molecular characteristics of cancer and normal stem cells - identification of targets for novel therapeutics and therapeutic strategies
MUNI/E/0128/2009, interní kód MU
Name: Úloha komponent Wnt/PCP dráhy v patogenezi B lymfocytární chronické leukémie
Investor: Masaryk University, Category E - development project + specific research
NT11217-5/2010, interní kód MU
Name: Úloha nekanonické Wnt signalizace v molekulární patogenezi chronické lymfocytární leukémie
Investor: Ministry of Health of the CR
1658, interní kód MU
Name: EMBO Young Investigator Programme (Acronym: EMBO)
Investor: EMBO (European Molecular Biology Organization), EMBO Young Investigator Programme