Antibodies against highly conserved sites in the epidermal growth factor receptor tyrosine kinase domain as probes for structure and function.
Antibodies against highly conserved sites in the epidermal growth factor receptor tyrosine kinase domain as probes for structure and function.
复制标题
针对表皮生长因子受体酪氨酸激酶结构域中高度保守位点的抗体，作为结构和功能的探针。
DOI：
10.1021/bi00068a025
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发表时间：
1993
期刊：
影响因子：
2.9
通讯作者：
Clinton,GM
中科院分区：
文献类型：
--
作者：
Brown,NA;Compton,LA;Clinton,GM
Revised Manuscript Received February 19, 1993 abstract: We generated anti-peptide antibodies against four highly conserved sequences in the kinase domain and against two nonconserved sequences surrounding autophosphorylation sites in the carboxylterminal domain of the epidermalgrowth factor receptor (EGFR). These antibodies were used to examine topology and function in catalysis of specific sequences. Two of the highly conserved sites, HRD (residues 811-818) and DFG (residues 827-838), appeared to participate in catalysissince aHRD and aDFG but not the other anti-peptide antibodies inhibited EGFR kinase activity. Examination of the topology of the six sites revealed that epitopes in all except the HRD site appeared to be exposed to antibody binding in the EGFR. The conditionsthat caused increased exposure of the HRD site to interaction with antibody included autophosphorylation, addition of the ionic detergent sodium dodecyl sulfate (SDS), and elevation in temperature from 4 to 34 C.Protein kinases are a large group of regulatory enzymes that play pivotal roles in signal transduction (Cohen, 1986; Hanks & Quinn, 1991). Theseenzymes are usually inactive until stimulated by their effectors. One mechanism by which protein kinases may be maintained in an inactive state is by blockage of the active site by regulatory regions of the protein which may mimic the substrate (Corbin et al., 1978; Pearson et al., 1988; Hardie, 1988).
