Negative growth control by a novel low M(r) phosphotyrosine protein phosphatase in normal and transformed cells.
Having determined the complete amino acid sequence of a cytosolic phosphatase purified from bovine liver, we studied the role of this enzyme (referred to as 'PTPase') in the control of cell proliferation. We used NIH/3T3 fibroblasts, both normal and transformed by the oncogenes v-erbB, v-src, and v-raf: a synthetic gene coding for PTPase was transfected into, and overexpressed in, normal and transformed NIH/3T3 cells with resulting inhibition of cell growth. Inhibition of proliferation correlated with the level of foreign PTPase; growth in soft agar was also inhibited in transformants overexpressing the enzyme. However, PTPase overexpression did not inhibit the rapid turnover of inositol lipids stimulated by platelet-derived growth factor. We conclude that this novel PTPase is active on cell type-specific signalling substrates that control normal and transformed fibroblast proliferation.
Ruggiero
M
M
Institute of General Pathology, University of Firenze, Italy.
Pazzagli
C
C
Rigacci
S
S
Magnelli
L
L
Raugei
G
G
Berti
A
A
Chiarugi
V P
VP
Pierce
J H
JH
Camici
G
G
Ramponi
G
G
D016475:3T3 Cells; D000818:Animals; D002455:Cell Division; D002461:Cell Line, Transformed; D015870:Gene Expression; D016391:Genes, src; D007295:Inositol Phosphates / Q000378:metabolism; D051379:Mice; D018739:Oncogene Proteins v-erbB; D027384:Oncogene Proteins v-raf; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics*; D014162:Transfection
D007295:Inositol Phosphates; D018739:Oncogene Proteins v-erbB; D010982:Platelet-Derived Growth Factor; D015682:Retroviridae Proteins, Oncogenic; D027384:Oncogene Proteins v-raf; D017027:Protein Tyrosine Phosphatases