TY - JOUR
T1 - Regulation of Vav localization in membrane rafts by adaptor molecules Grb2 and BLNK
AU - Johmura, Sachiko
AU - Oh-hora, Masatsugu
AU - Inabe, Kazunori
AU - Nishikawa, Yumiko
AU - Hayashi, Katsuhiko
AU - Vigorito, Elena
AU - Kitamura, Daisuke
AU - Turner, Martin
AU - Shingu, Koh
AU - Hikida, Masaki
AU - Kurosaki, Tomohiro
N1 - Funding Information:
We would like to thank our colleagues A. Weiss, L.E. Samelson, and J. Downward for providing us with human Vav1, human LAT, and GST-CRIB expression plasmids, respectively, T. Nakamoto and M. Kurosaki for expert technical assistance, and A. Kosugi for valuable advice. This work was supported by grants to T.K. from the Ministry of Education, Science, Sports, and Culture in Japan, the NOVARTIS Foundation, the Uehara Foundation, the Hoh-ansha Foundation, and the Human Frontier Science Program, and by a grant to M.T. from the Biotechnology and Biological Sciences Research Council in the UK.
PY - 2003/6/1
Y1 - 2003/6/1
N2 - Despite the importance of the Vav family proteins for B cell receptor (BCR) signaling, their activation mechanisms remain poorly understood. We demonstrate here that adaptor molecules Grb2 and BLNK, in addition to Vav, are required for efficient Rac1 activation in response to BCR stimulation. Loss of either Grb2 or BLNK results in decreased translocation of Vav3 to membrane rafts. By expression of Vav3 as a raft-targeted construct, the defective Rac1 activation in Grb2- or BLNK-deficient B cells is restored. Hence, our findings suggest that Grb2 and BLNK cooperate to localize Vav into membrane rafts, thereby contributing to optimal activation of Vav in B cells.
AB - Despite the importance of the Vav family proteins for B cell receptor (BCR) signaling, their activation mechanisms remain poorly understood. We demonstrate here that adaptor molecules Grb2 and BLNK, in addition to Vav, are required for efficient Rac1 activation in response to BCR stimulation. Loss of either Grb2 or BLNK results in decreased translocation of Vav3 to membrane rafts. By expression of Vav3 as a raft-targeted construct, the defective Rac1 activation in Grb2- or BLNK-deficient B cells is restored. Hence, our findings suggest that Grb2 and BLNK cooperate to localize Vav into membrane rafts, thereby contributing to optimal activation of Vav in B cells.
UR - http://www.scopus.com/inward/record.url?scp=0038094512&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0038094512&partnerID=8YFLogxK
U2 - 10.1016/S1074-7613(03)00139-0
DO - 10.1016/S1074-7613(03)00139-0
M3 - Article
C2 - 12818159
AN - SCOPUS:0038094512
SN - 1074-7613
VL - 18
SP - 777
EP - 787
JO - Immunity
JF - Immunity
IS - 6
ER -
