Soluble Epidermal Growth Factor Receptor: A Biomarker of Epithelial Ovarian Cancer
Soluble Epidermal Growth Factor Receptor: A Biomarker of Epithelial Ovarian Cancer
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DOI：
10.1007/978-0-387-98094-2_9
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发表时间：
2009-01-01
期刊：
影响因子：
--
通讯作者：
Maihle, Nita J.
中科院分区：
文献类型：
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作者：
Baron, Andre T.;Lafky, Jacqueline M.;Maihle, Nita J.
表皮生长因子受体(EGFR)是ErbB受体酪氨酸激酶家族的典型成员，包括ErbB1(EGFR)、ErbB2(HER2，Neu)、ErbB3(HER3)和ErbB4(HER4)。1-3生化和结构研究表明，EGFR的成熟形式是一种170 kDa的质膜蛋白，由胞外区、跨膜区和胞内区组成。4胞外区分为四个亚区：亚区I和亚区III与生长因子结合，亚区II和亚区IV通过半胱氨酸残基赋予胞外区二级和三级结构。细胞内结构域也被划分为亚域：酪氨酸激酶亚域和包括几个酪氨酸自动磷酸化位点的羧基末端调节亚结构域。一般来说，生长因子与EGFR结合导致ErbB受体家族任何成员的受体二聚化，酪氨酸残基的转磷酸化，大量含有SH2或PTB基序的细胞质蛋白的对接，以及蛋白磷酸化级联反应(例如，Ras-Raf-MAP激酶或PI-3激酶)。这些级联反应的激活反过来影响基因表达、细胞增殖和存活，以及细胞形状、粘附性和运动性的变化。5、6因此，EGFR在正常细胞的增殖、存活和分化中起着重要作用。7、8除了全长的EGFR外，细胞还通过交替的mRNA加工合成“可溶”的EGFR(可溶性表皮生长因子受体；sEGFR)亚型。这些sEGFR亚型只包含细胞外域的成分，因此是分泌的。替代EGFR转录本
The epidermal growth factor receptor (EGFR) is the prototypic member of the ErbB receptor tyrosine kinase family, which includes ErbB1 (EGFR), ErbB2 (HER2, Neu), ErbB3 (HER3), and ErbB4 (HER4). 1–3 Biochemical and structural studies show that the mature form of EGFR is a 170-kDa plasma membrane protein that is composed of extracellular, transmembrane-spanning, and intracellular domains. 4 The extracellular domain is divided into four subdomains: subdomains I and III function in growth factor binding, and subdomains II and IV confer secondary and tertiary structure to the extracellular domain through cysteine residues. The intracellular domain also is divided into subdomains: a tyrosine kinase subdomain and a carboxy-terminal regulatory subdomain that includes several tyrosine autophosphorylation sites. In general, growth factor binding to EGFR results in receptor dimerization with any member of the ErbB receptor family, transphosphorylation of tyrosine residues, docking of numerous cytoplasmic proteins containing either SH2 or PTB motifs, and activation of protein phosphorylation cascades (eg, Ras-Raf-MAP kinase or PI-3 kinase). Activation of these cascades, in turn, effect gene expression, cellular proliferation and survival, and changes in cell shape, adhesion, and motility. 5, 6 Consequently, EGFR plays an important role in normal cellular proliferation, survival, and differentiation. 7, 8 In addition to the full-length EGFR, cells synthesize ‘‘soluble’’isoforms of EGFR (soluble epidermal growth factor receptor; sEGFR) by alternative mRNA processing. These sEGFR isoforms contain only elements of the extracellular domain and, therefore, are secreted. Alternative EGFR transcripts