四跨膜蛋白（Tetraspannin）是一种细胞死亡的触发因子，同时也是肿瘤治疗的潜在靶点。5月14日国际肿瘤学著名杂志Cancer Cell发表了俄亥俄州立大学John C. Byrd领导的研究小组的研究论文“Tetraspanin CD37 Directly Mediates Transduction of Survival and Apoptotic Signals”。
该研究首次证实，在通常情况下表达于成熟或转化后B细胞表面的Tetraspanin家族成员CD37分子，可以通过相互连接激活酪氨酸的磷酸化。这一磷酸化事件使CD37与邻近的信息分子联系在一起，进而引发细胞凋亡级联反应。
更有趣的是，研究者同时发现了CD37分子上的两个具有相反调控功能的酪氨酸位点：一个位于N末端“免疫受体酪氨酸抑制基序（ITIM）样”基序区域，介导SHP1依赖的死亡；另一个位于C末端的“免疫受体酪氨酸激活基序（ITAM）样”基序区域，通过介导磷脂酰环己六醇-3-激酶依赖的存活来拮抗死亡信号。（生物谷Bioon.com）
doi:10.1016/j.ccr.2012.03.040
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PMID:
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.
