Author/Authors :
Lapalombella، نويسنده , , Rosa C. Yeh، نويسنده , , Yuh-Ying and Wang، نويسنده , , Liwen and Ramanunni، نويسنده , , Asha and Rafiq، نويسنده , , Sarwish and Jha، نويسنده , , Shruti and Staubli، نويسنده , , Justin and Lucas، نويسنده , , David M. and Mani، نويسنده , , Rajeswaran and Herman، نويسنده , , Sarah E.M. and Johnson، نويسنده , , Amy J. and Lozanski، نويسنده , , Arletta and Andritsos، نويسنده , , Leslie N. Jones ، نويسنده , , Jeffrey C. Flynn، نويسنده , , Joseph M. and Lannutti، نويسنده , , Brian and Thompson، نويسنده , , Peter and Algate، نويسنده , , Paul and Stromatt، نويسنده , , Scott and Jarjoura، نويسنده , , David and Mo، نويسنده , , Xiaokui and Wang، نويسنده , , Dasheng and Chen، نويسنده , , Ching-Shih and Lozanski، نويسنده , , Gerard and Heerema، نويسنده , , Nyla A. and Tridandapani، نويسنده , , Susheela and Freitas، نويسنده , , Michael A. and Muthusamy، نويسنده , , Natarajan and Byrd، نويسنده , , John C.، نويسنده ,
Abstract :
Summary
panins are commonly believed to act only as “molecular facilitators,” with no direct role in signal transduction. We herein demonstrate that upon ligation, CD37, a tetraspanin molecule expressed on mature normal and transformed B cells, becomes tyrosine phosphorylated, associates with proximal signaling molecules, and initiates a cascade of events leading to apoptosis. Moreover, we have identified two tyrosine residues with opposing regulatory functions: one lies in the N-terminal domain of CD37 in a predicted “ITIM-like” motif and mediates SHP1-dependent death, whereas the second lies in a predicted “ITAM motif” in the C-terminal domain of CD37 and counteracts death signals by mediating phosphatidylinositol 3-kinase-dependent survival.
