Showing papers by "Massimo Santoro published in 1994"

Molecular characterization of RET/PTC3; A novel rearranged version of the RETproto-oncogene in a human thyroid papillary carcinoma

Abstract: The RET proto-oncogene encodes a transmembrane receptor of the tyrosine kinase family and has frequently been found activated in human thyroid carcinomas of the papillary subtype. In most cases the activation consisted of the fusion of its tyrosine-kinase domain with the 5'-terminal region of a gene designated H4 or D10S170. We have named the resulting H4/RET chimeric oncogene RET/PTC. Another activated form of the RET oncogene has subsequently been found in a thyroid carcinoma and is now referred to as RET/PTC2. Here we report the identification and cloning of a novel rearranged version of the RET oncogene in a human thyroid papillary carcinoma. In this case the tyrosine-kinase domain of RET was fused to a sequence 790 bp long belonging to a new gene that we have named RFG (RET Fused Gene). This novel chimeric oncogene has been designated RET/PTC3. In order to have more insights into the function of RFG we have completely cloned and sequenced its cDNA. RFG predicted amino-acid sequence does not have any significant homology to any already known genes and is ubiquitously expressed in human and mouse tissues. Finally we provide evidence indicating that the rearrangement leading to the generation of RET/PTC3 occurred in vivo in the original tumor DNA.

RON is a heterodimeric tyrosine kinase receptor activated by the HGF homologue MSP.

Abstract: RON, a cDNA homologous to the hepatocyte growth factor (HGF) receptor gene (MET), encodes a putative tyrosine kinase. Here we show that the RON gene is expressed in several epithelial tissues as well as in granulocytes and monocytes. The major RON transcript is translated into a glycosylated single chain precursor, cleaved into a 185 kDa heterodimer (p185RON) of 35 (alpha) and 150 kDa (beta) disulfide-linked chains, before exposure at the cell surface. The Ron beta-chain displays intrinsic tyrosine kinase activity in vitro, after immunoprecipitation by specific antibodies. In vivo, tyrosine phosphorylation of p185RON is induced by stimulation with macrophage stimulating protein (MSP), a protease-like factor containing four 'kringle' domains, homologous to HGF. In epithelial cells, MSP-induced tyrosine phosphorylation of p185RON is followed by DNA synthesis. p185RON is not activated by HGF, nor is the HGF receptor activated by MSP in biochemical and biological assays. p185RON is also activated by a pure recombinant protein containing only the N-terminal two kringles of MSP. These data show that p185RON is a tyrosine kinase activated by MSP and that it is member of a family of growth factor receptors with distinct specificities for structurally related ligands.