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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F22%3A00569246" target="_blank" >RIV/68081707:_____/22:00569246 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00159816:_____/22:00076170 RIV/00216224:14310/22:00125590 RIV/65269705:_____/22:00076170

Výsledek na webu

<a href="https://www.frontiersin.org/articles/10.3389/fcell.2022.838871/full" target="_blank" >https://www.frontiersin.org/articles/10.3389/fcell.2022.838871/full</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fcell.2022.838871" target="_blank" >10.3389/fcell.2022.838871</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10601 - Cell biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Frontiers in Cell and Developmental Biology

ISSN

2296-634X

e-ISSN

2296-634X

Svazek periodika

9

Číslo periodika v rámci svazku

FEB 28 2022

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

11

Strana od-do

838871

Kód UT WoS článku

000896044000001

EID výsledku v databázi Scopus

2-s2.0-85126728312