J 2022

Lyn Phosphorylates and Controls ROR1 Surface Dynamics During Chemotaxis of CLL Cells

DAVE, Zankruti, Olga VONDÁLOVÁ BLANÁŘOVÁ, Štěpán ČADA, Pavlína JANOVSKÁ, Nikodém ZEZULA et. al.

Basic information

Original name

Lyn Phosphorylates and Controls ROR1 Surface Dynamics During Chemotaxis of CLL Cells

Authors

DAVE, Zankruti (356 India, belonging to the institution), Olga VONDÁLOVÁ BLANÁŘOVÁ (203 Czech Republic, belonging to the institution), Štěpán ČADA (203 Czech Republic, belonging to the institution), Pavlína JANOVSKÁ (203 Czech Republic, belonging to the institution), Nikodém ZEZULA (203 Czech Republic, belonging to the institution), Martin BĚHAL (203 Czech Republic, belonging to the institution), Kateřina HANÁKOVÁ (203 Czech Republic, belonging to the institution), Sri Ranjani GANJI (356 India, belonging to the institution), Pavel KREJČÍ (203 Czech Republic, belonging to the institution), Kristína GÖMÖRYOVÁ (703 Slovakia, belonging to the institution), Helena PESCHELOVÁ (203 Czech Republic, belonging to the institution), Michal ŠMÍDA (203 Czech Republic, belonging to the institution), Zbyněk ZDRÁHAL (203 Czech Republic, belonging to the institution), Šárka PAVLOVÁ (203 Czech Republic, belonging to the institution), Jana KOTAŠKOVÁ (203 Czech Republic, belonging to the institution), Šárka POSPÍŠILOVÁ (203 Czech Republic, belonging to the institution) and Vítězslav BRYJA (203 Czech Republic, guarantor, belonging to the institution)

Edition

Frontiers in Cell and Developmental Biology, Frontiers Media SA, 2022, 2296-634X

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10605 Developmental biology

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 5.500

RIV identification code

RIV/00216224:14310/22:00125590

Organization unit

Faculty of Science

UT WoS

000896044000001

Keywords in English

Ror1; Lyn; crosstalk; phosphorylation; CLL; BCR; signaling pathway

Tags

International impact, Reviewed
Změněno: 15/10/2024 14:33, Ing. Martina Blahová

Abstract

V originále

Chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) are malignancies characterized by the dependence on B-cell receptor (BCR) signaling and by the high expression of ROR1, the cell surface receptor for Wnt-5a. Both, BCR and ROR1 are therapeutic targets in these diseases and the understanding of their mutual cross talk is thus of direct therapeutic relevance. In this study we analyzed the role of Lyn, a kinase from the Src family participating in BCR signaling, as a mediator of the BCR-ROR1 crosstalk. We confirm the functional interaction between Lyn and ROR1 and demonstrate that Lyn kinase efficiently phosphorylates ROR1 in its kinase domain and aids the recruitment of the E3 ligase c-CBL. We show that ROR1 surface dynamics in migrating primary CLL cells as well as chemotactic properties of CLL cells were inhibited by Lyn inhibitor dasatinib. Our data establish Lyn-mediated phosphorylation of ROR1 as a point of crosstalk between BCR and ROR1 signaling pathways.

Links

EF16_025/0007381, research and development project
Name: Preklinická progrese nových organických sloučenin s cílenou biologickou aktivitou
EF18_046/0015974, research and development project
Name: Modernizace České infrastruktury pro integrativní strukturní biologii
GA17-09525S, research and development project
Name: Neobvyklé signální dráhy lidských receptorových tyrozinových kináz
Investor: Czech Science Foundation
GA17-16680S, research and development project
Name: Nové postupy pro určení aktivity dráhy planární buněčné polarity (PCP)
Investor: Czech Science Foundation
GA19-20123S, research and development project
Name: Regulace časného vývoje savčí končetiny pomocí nestabilních morfogenů z rodiny FGF (Acronym: Regulace časného vývoje savčí končetiny)
Investor: Czech Science Foundation
LM2018127, research and development project
Name: Česká infrastruktura pro integrativní strukturní biologii (Acronym: CIISB)
Investor: Ministry of Education, Youth and Sports of the CR
LM2018140, research and development project
Name: e-Infrastruktura CZ (Acronym: e-INFRA CZ)
Investor: Ministry of Education, Youth and Sports of the CR
608180, interní kód MU
Name: WNT-mediated signal relay in stem cells and oncogenesis - from basic biology to applications (Acronym: WntsApp)
Investor: European Union, WNT-mediated signal relay in stem cells and oncogenesis - from basic biology to applications, People
90127, large research infrastructures
Name: CIISB II
90132, large research infrastructures
Name: NCMG II