A SINGLE AMINO-ACID SUBSTITUTION IS SUFFICIENT TO MODIFY THE MITOGENIC PROPERTIES OF THE EPIDERMAL GROWTH-FACTOR RECEPTOR TO RESEMBLE THAT OF GP185(ERBB-2)

被引：33

作者：

DIFIORE, PP ^{[1
]}

HELIN, K ^{[1
]}

KRAUS, MH ^{[1
]}

PIERCE, JH ^{[1
]}

ARTRIP, J ^{[1
]}

SEGATTO, O ^{[1
]}

BOTTARO, DP ^{[1
]}

机构：

[1] REGINA ELENA INST CANC RES,I-00158 ROME,ITALY

来源：

EMBO JOURNAL | 1992年 / 11卷 / 11期

关键词：

EGFR; ERBB-2; SUBSTRATES; SIGNAL TRANSDUCTION; TYROSINE KINASES;

D O I：

10.1002/j.1460-2075.1992.tb05486.x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The epidermal growth factor (EGF) receptor (EGFR) and the erbB-2 gene product, gp185erbB-2, exhibit distinct abilities to stimulate mitogenesis in different target cells. By using chimeric molecules between these two receptors, we have previously shown that their intracellular juxta-membrane regions are responsible for this specificity. Here we describe a genetically engineered EGFR mutant containing a threonine for arginine substitution at position 662 in the EGFR juxtamembrane domain, corresponding to threonine 694 in gp185erbB-2. This mutant, designated EGFR(Thr662), displayed affinity for EGF binding and catalytic properties that were indistinguishable from those of the wild type EGFR. However, EGFR(Thr662) behaved much as gp185erbB-2 in a number of bioassays which readily distinguish between the mitogenic effects of EGFR and gp185erbB-2. Moreover, significant differences were detected in the pattern of intracellular proteins phosphorylated on tyrosine in vivo by EGFR and EGFR(Thr662) in response to EGF. Thus, small differences in the primary sequence of two closely related receptors have dramatic effects on their ability to couple with mitogenic pathways.

引用

页码：3927 / 3933

页数：7

共 26 条

[11] THE ERBB-2 MITOGENIC SIGNALING PATHWAY - TYROSINE PHOSPHORYLATION OF PHOSPHOLIPASE-C-GAMMA AND GTPASE-ACTIVATING PROTEIN DOES NOT CORRELATE WITH ERBB-2 MITOGENIC POTENCY [J].