Identification of type I receptors for osteogenic protein-1 and bone morphogenetic protein-4.
Identification of type I receptors for osteogenic protein-1 and bone morphogenetic protein-4.
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发表时间：
1994-06
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通讯作者：
P. Dijke;Hidetoshi Yamashitas;-T.;Kuber Sampathfl;Reddill;Miguel Estevez;Donald;-L.;Riddle
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作者：
P. Dijke;Hidetoshi Yamashitas;-T.;Kuber Sampathfl;Reddill;Miguel Estevez;Donald;-L.;Riddle
骨形态发生蛋白（BMPs）是一种多功能蛋白质，在结构上与转化生长因子-β（TGF-β）和激活素相关。TGF-β和激活素通过形成I型和II型丝氨酸/苏氨酸激酶受体的异聚体复合物发挥作用。我们先前已经鉴定了一系列I型丝氨酸/苏氨酸激酶受体，称为激活素受体样激酶（ALK）-1至-6。ALK-5是TGF-β I型受体，而ALK-2和ALK-4是激活素I型受体。在这里，我们研究了BMP家族中的蛋白质与ALK的结合。在转染的COS细胞中，在不存在II型受体的情况下观察到成骨蛋白（OP）-1和BMP-4与某些ALK的结合，并且在共转染来自秀丽隐杆线虫的BMP II型受体后，它们的结合增加。OP-1与ALK-2和ALK-6有效结合，与ALK-3的结合效率较低，而BMP-4与ALK-3和ALK-6有效结合。类似地，OP-1在各种未转染细胞系中与ALK-2、ALK-3和/或ALK-6结合，尽管不同细胞类型之间的结合特征不同。BMP-4在MC 3 T3-E1成骨细胞和人包皮成纤维细胞中与ALK-3结合。这些结果表明，ALK-3和ALK-6是OP-1和BMP-4的I型受体;此外，ALK-2是激活素和OP-1共有的I型受体，但不是BMP-4共有的I型受体。
Bone morphogenetic proteins (BMPs) are multifunctional proteins, structurally related to transforming growth factor-beta (TGF-beta) and activin. TGF-beta and activin exert their effects by forming heteromeric complexes of type I and type II serine/threonine kinase receptors. We have previously identified a series of type I serine/threonine kinase receptors, termed activin receptor-like kinase (ALK)-1 to -6. ALK-5 is a TGF-beta type I receptor, whereas ALK-2 and ALK-4 are activin type I receptors. Here we investigated the binding of proteins in the BMP family to ALKs. In transfected COS cells, the binding of osteogenic protein (OP)-1 and BMP-4 to certain ALKs was observed in the absence of type II receptors, and their binding was increased after co-transfection of a BMP type II receptor from Caenorhabditis elegans, DAF-4. OP-1 bound to ALK-2 and ALK-6 efficiently, and to ALK-3 less efficiently, whereas BMP-4 bound to ALK-3 and ALK-6 efficiently. Similarly, OP-1 bound to ALK-2, ALK-3, and/or ALK-6 in various nontransfected cell lines, although the binding profiles were different between different cell types. BMP-4 bound to ALK-3 in MC3T3-E1 osteoblasts and human foreskin fibroblasts. These results suggest that ALK-3 and ALK-6 are type I receptors for OP-1 and BMP-4; in addition, ALK-2 is a type I receptor shared by activin and OP-1, but not by BMP-4.