BLNK mediates Syk-dependent Btk activation

Citation
Y. Baba et al., BLNK mediates Syk-dependent Btk activation, P NAS US, 98(5), 2001, pp. 2582-2586
Citations number
32
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN journal
0027-8424 → ACNP
Volume
98
Issue
5
Year of publication
2001
Pages
2582 - 2586
Database
ISI
SICI code
0027-8424(20010227)98:5<2582:BMSBA>2.0.ZU;2-D
Abstract
Btk is a critical molecule in B cell antigen receptor (BCR)-coupled signali ng, and its activity is regulated by Lyn and Syk. Although the molecular me chanism of Lyn-dependent Btk activation has been investigated, that of Syk- dependent Btk activation has remained unidentified. We have demonstrated th at BLNK mediates Syk-dependent Btk activation. In a reconstitution cell sys tem, coexpression of BLNK allows Syk to phosphorylate Btk on its tyrosine 5 51, leading to the enhancement of Btk activity. This phosphorylation depend s on the interaction of Btk and BLNK by means of the Btk-Src homology 2 dom ain. The existence of such an activation mechanism is supported by the obse rvation that the BCR-induced Btk phosphorylation and activation are signifi cantly reduced in BLNK-deficient B cells as well as in Syk-deficient B cell s. Although previous observations have identified the function of BLNK as t he linker that integrates the action of Btk and Syk into downstream effecte rs such as phospholipase C gamma2, our present study indicates another func tion of BLNK that connects the activity of Syk to that of Btk.