Suppression of v-fms-induced transformation by overexpression of a truncated T-cell protein tyrosine phosphatase.
Rat 2 cells stably transformed by murine v-fms (pB5 cells) were infected with retroviruses containing a human cDNA encoding either a full-length human T-cell protein tyrosine phosphatase (TC.PTP) or a truncated form (delta C11.PTP) in which an 11-kDa carboxy-terminal extension had been removed. This segment is responsible for enzyme localization and regulation. Clonal cell lines were isolated following G418 selection and their transforming properties analysed; pB5 cells containing the vector alone or TC.PTP remained transformed. These cells grew readily in soft agar, formed tumors in nude mice and were morphologically indistinguishable from the parental pB5 cells. In contrast, cells expressing delta C11.PTP showed dramatic changes in cell morphology, loss of anchorage-independent growth in soft agar and reduced or lack of tumor formation in nude mice. Both increases and decreases in tyrosine phosphorylation of specific proteins in the cells overexpressing the truncated enzyme were detected. These results indicate that coexpression of the deregulated, soluble tyrosine phosphatase with a constitutively active, oncogenic receptor tyrosine kinase leads to the suppression of the transformed phenotype.
Zander
N F
NF
Department of Biochemistry, University of Washington, Seattle 98195.
Cool
D E
DE
Diltz
C D
CD
Rohrschneider
L R
LR
Krebs
E G
EG
Fischer
E H
EH
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D016236:Genes, fms; D019000:Phosphotyrosine; D017027:Protein Tyrosine Phosphatases / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D013601:T-Lymphocytes / Q000201:enzymology*; D014162:Transfection; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
D019000:Phosphotyrosine; D014443:Tyrosine; D017027:Protein Tyrosine Phosphatases