TY - JOUR
T1 - A RING finger motif regulates transforming activity of the rfp/ret fusion gene
AU - Hasegawa, Nakaba
AU - Iwashita, Toshihide
AU - Asai, Naoya
AU - Murakami, Hideki
AU - Iwata, Yosuke
AU - Isomura, Takeshi
AU - Goto, Hidemi
AU - Hayakawa, Tetsuo
AU - Takahashi, Masahide
N1 - Funding Information:
This work was supported in part by Grants-in Aid for Scientific Research and for Cancer Research from the Ministry of Education, Science and Culture of Japan and by a grant from the Mitsukoshi Foundation.
PY - 1996/8/14
Y1 - 1996/8/14
N2 - The rfp/ret transforming gene was generated by DNA rearrangement which occurred during transfection of NIH 3T3 cells. The amino-terminal half of Rfp with a RING finger motif was fused to the truncated Ret receptor tyrosine kinase, leading to a transforming sequence, Rfp/Ret. In the present study, to elucidate the importance of a RING finger motif for its transforming activity, we mutated cysteine or histidine residues present in the motif that are believed to be crucial for the tertiary structure of the protein. Substitution of Cys-16, Cys-31, or His-33 markedly decreased the transforming activity of Rfp/Ret. These mutations also resulted in a striking decrease of tyrosine phosphorylation of the mutant proteins in transfectants. In contrast, mutations of Cys-118 or His-124 in the second cysteine/histidine-rich motif (called B box) of Rfp/Ret did not affect its activity. These results thus indicated that the RING finger structure is critical for the full transforming activity of Rfp/Ret.
AB - The rfp/ret transforming gene was generated by DNA rearrangement which occurred during transfection of NIH 3T3 cells. The amino-terminal half of Rfp with a RING finger motif was fused to the truncated Ret receptor tyrosine kinase, leading to a transforming sequence, Rfp/Ret. In the present study, to elucidate the importance of a RING finger motif for its transforming activity, we mutated cysteine or histidine residues present in the motif that are believed to be crucial for the tertiary structure of the protein. Substitution of Cys-16, Cys-31, or His-33 markedly decreased the transforming activity of Rfp/Ret. These mutations also resulted in a striking decrease of tyrosine phosphorylation of the mutant proteins in transfectants. In contrast, mutations of Cys-118 or His-124 in the second cysteine/histidine-rich motif (called B box) of Rfp/Ret did not affect its activity. These results thus indicated that the RING finger structure is critical for the full transforming activity of Rfp/Ret.
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U2 - 10.1006/bbrc.1996.1221
DO - 10.1006/bbrc.1996.1221
M3 - Article
C2 - 8753810
AN - SCOPUS:0030583287
SN - 0006-291X
VL - 225
SP - 627
EP - 631
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -