四跨膜蛋白（Tetraspannin）是一種細胞死亡的觸發(fā)因子,，同時也是腫瘤治療的潛在靶點,。5月14日國際腫瘤學(xué)著名雜志Cancer Cell發(fā)表了俄亥俄州立大學(xué)John C. Byrd領(lǐng)導(dǎo)的研究小組的研究論文“Tetraspanin CD37 Directly Mediates Transduction of Survival and Apoptotic Signals”,。
該研究首次證實,，在通常情況下表達于成熟或轉(zhuǎn)化后B細胞表面的Tetraspanin家族成員CD37分子,，可以通過相互連接激活酪氨酸的磷酸化,。這一磷酸化事件使CD37與鄰近的信息分子聯(lián)系在一起，進而引發(fā)細胞凋亡級聯(lián)反應(yīng),。
更有趣的是,，研究者同時發(fā)現(xiàn)了CD37分子上的兩個具有相反調(diào)控功能的酪氨酸位點：一個位于N末端“免疫受體酪氨酸抑制基序（ITIM）樣”基序區(qū)域，介導(dǎo)SHP1依賴的死亡,；另一個位于C末端的“免疫受體酪氨酸激活基序（ITAM）樣”基序區(qū)域,，通過介導(dǎo)磷脂酰環(huán)己六醇-3-激酶依賴的存活來拮抗死亡信號。（生物谷Bioon.com）
doi:10.1016/j.ccr.2012.03.040
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Tetraspanin CD37 Directly Mediates Transduction of Survival and Apoptotic Signals
Rosa Lapalombella1, Yuh-Ying Yeh1, Liwen Wang2, Asha Ramanunni1, Sarwish Rafiq1, 3, Shruti Jha1, Justin Staubli1, 3, David M. Lucas1, 5, Rajeswaran Mani1, 4, Sarah E.M. Herman1, 3, Amy J. Johnson1, 5, Arletta Lozanski1, Leslie Andritsos1, Jeffrey Jones1, Joseph M. Flynn1, Brian Lannutti10, Peter Thompson11, Paul Algate12, Scott Stromatt12, David Jarjoura6, Xiaokui Mo6, Dasheng Wang5, Ching-Shih Chen1, 5, Gerard Lozanski7, Nyla A. Heerema7, Susheela Tridandapani8, Michael A. Freitas9, 13, Natarajan Muthusamy1, 4, 9, 13, , and John C. Byrd
Tetraspanins 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.
