Endoglin is an accessory protein that interacts with the signaling receptor complex of multiple members of the transforming growth factor-β superfamily
Endoglin is an accessory protein that interacts with the signaling receptor complex of multiple members of the transforming growth factor-β superfamily
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DOI：
10.1074/jbc.274.2.584
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发表时间：
1999-01-08
影响因子：
4.8
通讯作者：
Letarte, M
中科院分区：
文献类型：
--
作者：
Barbara, NP;Wrana, JL;Letarte, M
内皮糖蛋白（CD 105）是一种跨膜糖蛋白，结合转化生长因子（TGF）-β 1和β 3，并通过内皮细胞和白血病细胞的亲和标记与Ser/Thr激酶信号受体复合物共沉淀。目前的研究表明，除了TGF-β 1和β 3，内皮糖蛋白与激活素A，骨形态发生蛋白（BMP）-7，和BMP-2相互作用，但需要共同表达的配体结合激酶受体的这种协会。内皮糖蛋白自身不能结合配体，也不改变与激酶受体的结合。它通过与TGF-β II型受体结合而结合TGF-β 1和TGF-β 3，并通过激活素II型受体ActRII和ActBIIB与激活素A和BMP-7相互作用，无论共表达哪种I型受体伴侣。然而，内皮糖蛋白通过与配体结合I型受体ALK 3和ALK 6相互作用而结合BMP-2。异聚信号复合物的形成没有改变endoglin的存在下，虽然它与这些复合物共沉淀。内皮糖蛋白不通过含有BMP II型受体的复合物与BMP-7相互作用，证明其作用的特异性。我们的数据表明，endoglin是一个辅助蛋白的多激酶受体复合物的TGF-β超家族。
Endoglin (CD105) is a transmembrane glycoprotein that binds transforming growth factor (TGF)-beta 1 and -beta 3, and coprecipitates with the Ser/Thr kinase signaling receptor complex by affinity labeling of endothelial and leukemic cells. The present study shows that in addition to TGF-beta 1 and -beta 3, endoglin interacts with activin-A, bone morphogenetic protein (BMP)-7, and BMP-2 but requires coexpression of the respective ligand binding kinase receptor for this association. Endoglin cannot bind ligands on its own and does not alter binding to the kinase receptors. It binds TGF-beta 1 and -beta 3 by associating with the TGF-P type II receptor and interacts with activin-A and BMP-7 via activin type II receptors, ActRII and ActBIIB, regardless of which type I receptor partner is coexpressed. However, endoglin binds BMP-2 by interacting with the ligand binding type I receptors, ALK3 and ALK6. The formation of heteromeric signaling complexes was not altered by the presence of endoglin, although it was coprecipitated with these complexes. Endoglin did not interact with BMP-7 through complexes containing the BMP type II receptor, demonstrating specificity of its action. Our data suggest that endoglin is an accessory protein of multiple kinase receptor complexes of the TGF-beta superfamily.