Activin receptor-like kinases: a novel subclass of cell-surface receptors with predicted serine/threonine kinase activity.
Activin receptor-like kinases: a novel subclass of cell-surface receptors with predicted serine/threonine kinase activity.
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发表时间：
1993-10
期刊：
影响因子：
8
通讯作者：
P. tenDijke;H. Ichijo;P. Franzén;P. Schulz;J. Saras;H. Toyoshima;C. Heldin;K. Miyazono
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文献类型：
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作者：
P. tenDijke;H. Ichijo;P. Franzén;P. Schulz;J. Saras;H. Toyoshima;C. Heldin;K. Miyazono
采用聚合酶链反应（PCR）技术获得了编码4种新型跨膜蛋白丝氨酸/苏氨酸激酶的人cDNA克隆，分别命名为激活素受体样激酶（ALK）-1、-2、-3和-4。根据II型激活素受体与Daf-1之间的序列相似性设计PCR引物。ALK-1、ALK-2和ALK-3的cDNA克隆分别编码503、509和532个氨基酸的完整蛋白质。ALK-4 cDNA是不完整的，预测的383个氨基酸的蛋白质具有截短的胞外结构域。ALK具有相似的结构域结构，包括在N末端的预测信号序列，随后是亲水性富含半胱氨酸的配体结合结构域、单个疏水性跨膜区和几乎完全由推定的丝氨酸/苏氨酸激酶结构域组成的C末端细胞内部分。ALK与活化素受体II型和IIB型、转化生长因子-β（TGF-β）II型受体和激酶结构域中的Daf-1具有约40%的序列同一性。然而，ALK-1、ALK-2、ALK-3和ALK-4之间的序列同一性较高（60-79%），表明它们在推定的受体丝氨酸/苏氨酸激酶中形成一个亚家族。ALK的胞外结构域与其他推定的受体丝氨酸/苏氨酸激酶仅显示出很小的序列同一性，但半胱氨酸残基是保守的。它们的结构特性表明ALK-1至ALK-4是可结合TGF-β超家族成员配体的受体。不同ALK在人体组织中的mRNA表达各不相同; ALK-2和ALK-4显示普遍存在的组织表达模式，而ALK-1和ALK-3的分布在不同组织之间差异很大，表达模式更有限。这些结果表明，每种ALK可能具有不同的体内功能。
Human cDNA clones encoding four novel putative transmembrane protein serine/threonine kinases, denoted activin receptor-like kinase (ALK) -1, -2, -3 and -4, were obtained using a polymerase chain reaction (PCR)-based strategy. The PCR primers were designed based upon the sequence similarity between the activin receptor type II and Daf-1. The cDNA clones for ALK-1, -2 and -3 encode complete proteins of 503, 509 and 532 amino acids respectively. The ALK-4 cDNA is incomplete and the predicted protein of 383 amino acids has a truncated extracellular domain. The ALKs share similar domain structures, comprising predicted signal sequences at the N-terminals, followed by hydrophilic cysteine-rich ligand-binding domains, single hydrophobic transmembrane regions and C-terminal intracellular portions that consist almost entirely of putative serine/threonine kinase domains. The ALKs have approximately 40% sequence identity to activin receptors type II and IIB, transforming growth factor-beta (TGF-beta) type II receptor and Daf-1 in the kinase domains. However, the sequence identities are higher (60-79%) between ALK-1, -2, -3 and -4, suggesting that they form a subfamily among the putative receptor serine/threonine kinases. The extracellular domains of ALKs show only little sequence identity to other putative receptor serine/threonine kinases, but the cysteine residues are conserved. Their structural properties suggest that ALK-1 to -4 are receptors that may bind ligands that are members of the TGF-beta superfamily. The expression of mRNA in human tissues varied for the different ALKs; ALK-2 and ALK-4 showed ubiquitous tissue expression patterns, whereas the distribution of ALK-1 and ALK-3 varied strongly between different tissues with more restricted expression patterns. These results suggest that each ALK may have different in vivo functions.