Structural and Functional Properties of Platelet-Derived Growth Factor and Stem Cell Factor Receptors
Structural and Functional Properties of Platelet-Derived Growth Factor and Stem Cell Factor Receptors
复制标题
DOI：
10.1101/cshperspect.a009100
复制
发表时间：
2013-08-01
影响因子：
7.2
通讯作者：
Lennartsson, Johan
中科院分区：
文献类型：
--
作者：
Heldin, Carl-Henrik;Lennartsson, Johan
血小板衍生生长因子（PDGF）和干细胞因子（SCF）的受体是III型PTK受体的成员，其特征在于细胞外的五个Ig样结构域和细胞内的分裂激酶结构域。受体通过配体诱导的二聚化激活，导致特定酪氨酸残基的自磷酸化。因此，受体的激酶活性被激活，并产生下游SH 2结构域信号转导分子的对接位点;这些途径的激活促进细胞生长、存活和迁移。这些受体在胚胎发育过程中介导重要信号，并控制成体组织的稳态。它们的过度活性见于恶性肿瘤和其他涉及过度细胞增殖的疾病，如动脉粥样硬化和纤维化疾病。在癌症中，PDGF和SCF受体的突变-包括基因融合、点突变和扩增-驱动某些恶性肿瘤的亚群，如胃肠道间质瘤、慢性粒单核细胞白血病、嗜酸性粒细胞增多综合征、胶质母细胞瘤、急性髓性白血病、肥大细胞增多症和黑色素瘤。
The receptors for platelet-derived growth factor (PDGF) and stem cell factor (SCF) are members of the type III class of PTK receptors, which are characterized by five Ig-like domains extracellularly and a split kinase domain intracellularly. The receptors are activated by ligand-induced dimerization, leading to autophosphorylation on specific tyrosine residues. Thereby the kinase activities of the receptors are activated and docking sites for downstream SH2 domain signal transduction molecules are created; activation of these pathways promotes cell growth, survival, and migration. These receptors mediate important signals during the embryonal development, and control tissue homeostasis in the adult. Their overactivity is seen in malignancies and other diseases involving excessive cell proliferation, such as atherosclerosis and fibrotic diseases. In cancer, mutations of PDGF and SCF receptors-including gene fusions, point mutations, and amplifications-drive subpopulations of certain malignancies, such as gastrointestinal stromal tumors, chronic myelomonocytic leukemia, hypereosinophilic syndrome, glioblastoma, acute myeloid leukemia, mastocytosis, and melanoma.