AN EPIDERMAL GROWTH-FACTOR RECEPTOR RET CHIMERA GENERATES MITOGENIC AND TRANSFORMING SIGNALS - EVIDENCE FOR A RET-SPECIFIC SIGNALING PATHWAY

被引:122
作者
SANTORO, M
WONG, WT
AROCA, P
SANTOS, E
MATOSKOVA, B
GRIECO, M
FUSCO, A
DIFIORE, PP
机构
[1] UNIV NAPLES, FAC MED & CHIRURG 2, CNR, CTR ENDOCRINOL & ONCOL SPERIMENTALE, I-80131 NAPLES, ITALY
[2] UNIV NAPLES, FAC MED & CHIRURG 2, DIPARTIMENTO BIOL & PATOL CELLULARE & MOLEC L CALI, I-80131 NAPLES, ITALY
[3] UNIV REGGIO CALABRIA, FAC MED & CHIRURG CATANZARO, DIPARTIMENTO MED SPERIMENTALE & CLIN, I-88100 CATANZARO, ITALY
[4] NIDR, CELLULAR DEV & ONCOL, BETHESDA, MD 20892 USA
关键词
D O I
10.1128/MCB.14.1.663
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
A chimeric expression vector which encoded for a molecule encompassing the extracellular domain of the epidermal growth factor (EGF) receptor (EGFR) and the intracellular domain of the ret kinase (EGFR/ret chimera) was generated. Upon ectopic expression in mammalian cells, the EGFR/ret chimera was correctly synthesized and transported to the cell surface, where it was shown capable of binding EGF and transducing an EGF-dependent signal intracellularly. Thus, the EGFR/ret chimera allows us to study the biological effects and biochemical activities of the ret kinase under controlled conditions of activation. Comparative analysis of the growth-promoting activity of the EGFR/ret chimera expressed in fibroblastic or hematopoietic cells revealed a biological phenotype clearly distinguishable from that of the EGFR, indicating that the two kinases couple with mitogenic pathways which are different to some extent. Analysis of biochemical pathways implicated in the transduction of mitogenic signals also evidenced significant differences between the ret kinase and other receptor tyrosine kinases. Thus, the sum of our results indicates the existence of a ret-specific pathway of mitogenic signaling.
引用
收藏
页码:663 / 675
页数:13
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