摘要
表皮生长因子受体(EGFR)是一种170-kDa跨膜受体酪氨酸激酶。其配体,如:表皮生长因子(EGF)、转化生长因子-α(TGF-α),和受体胞外结构域结合可引发受体二聚化和聚集,继而导致受体胞内部分的酪氨酸激酶激活。这种激活的、聚集的受体可使聚集的其他受体磷酸化,产生可供带有SH2结构域的胞内蛋白结合的位点,引发其下游一系列信号转导途径的激活。EGFR是一个多效应的信息传递者,其激活后能促进有丝分裂或诱导细胞凋亡;增加细胞活性、蛋白质分泌;诱导细胞分化或细胞去分化。人类皮肤中对EGF/TGF-α的反应决定于EGFR的数量和位置,并受影响结合力、内吞、受体酪氨酸激酶活性等过程的调节。EGFR在组织中的分布与该组织的生长活性相一致。链脲佐菌素(Streptozotocin,STZ)诱导的糖尿病(STZ-DM)小鼠肝细胞中高亲和力位点的EGFR完全缺失,低亲和力位点下降到50000。糖尿病患者组织中EGFR的性质发生了改变,受体后自磷酸化程度下降。目前还不清楚这种改变与疾病发生的因果关系。
The epidermal growth factor receptor(EGFR) is a 170 kDa transmembrane receptor tyrosine kinase.EGFR ligands, such as EGF or transforming growth factor α, bind to the extracellular domain of the receptor and induce receptor dimerization and clustering; this in turn results in activation of the receptor's intracellular tyrosine kinase activity. The activated, clustered receptors transphosphorylate other co clustered receptors, creating binding sites for cellular proteins containing SH2 domains, and become activated to continue the signal transduction cascade.The integrated biological responses to EGFR signaling are pleiotropic including mitogenesis or apoptosis, enhanced cell motility,protein secretion, and differentiation or dedifferentiation. In human skin, the response to EGF/TGF alpha is determined by the location and number of receptors and is modulated by processes affecting the binding affinity,internalization, and tyrosine kinase activity of the receptor.The distribution of EGFR in tissue is correspondent with the growth activity of the tissue. Streptozotocin induced diabetes reduces the number of low affinity EGFR to 50,000 and produces a complete loss of high affinity sites in freshly isolated rat hepatocytes. In diabetic tissue, the quality of EGFR changes. And diabetes can reduce EGFR autophosphorylation too. It is not clear if the altered patterns reflect the consequence of the disease or are the cause of the disease.
出处
《中国临床康复》
CSCD
2003年第6期944-945,949,共3页
Chinese Journal of Clinical Rehabilitation
基金
国家973重点基础研究发展规划项目资助(G1999054205)
关键词
表皮生长因子
受体
糖尿病
伤口愈合
receptor,epidermal growth factor
diabetes mellitus
wound healing