scholarly journals Syp (SH-PTP2) is a positive mediator of growth factor-stimulated mitogenic signal transduction.

1994 ◽  
Vol 269 (33) ◽  
pp. 21244-21248
Author(s):  
S. Xiao ◽  
D.W. Rose ◽  
T. Sasaoka ◽  
H. Maegawa ◽  
T.R. Burke ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Growth Factor ◽  
Mitogenic Signal Transduction ◽  
Mitogenic Signal

Effect of a dominant inhibitory Ha-ras mutation on mitogenic signal transduction in NIH 3T3 cells

1990 ◽  
Vol 10 (10) ◽  
pp. 5314-5323
Author(s):  
H Cai ◽  
J Szeberényi ◽  
G M Cooper
Keyword(s):  
Signal Transduction ◽  
Protein Kinase C ◽  
Growth Factor ◽  
Protein Kinase ◽  
Dna Synthesis ◽  
3T3 Cells ◽  
Kinase C ◽  
Mitogenic Signal Transduction ◽  
Nih 3T3 ◽  
Mitogenic Signal

We used a dominant inhibitory mutation of c-Ha-ras which changes Ser-17 to Asn-17 in the gene product p21 [p21(Asn-17)Ha-ras] to investigate ras function in mitogenic signal transduction. An NIH 3T3 cell line [NIH(M17)] was isolated that displayed inducible expression of the mutant Ha-ras gene (Ha-ras Asn-17) via the mouse mammary tumor virus long terminal repeat and was growth inhibited by dexamethasone. The effect of dexamethasone induction on response of quiescent NIH(M17) cells to mitogens was then analyzed. Stimulation of DNA synthesis by epidermal growth factor (EGF) and 12-O-tetradecanoylphorbol-13-acetate (TPA) was completely blocked by p21(Asn-17) expression, and stimulation by serum, fibroblast growth factor, and platelet-derived growth factor was partially inhibited. However, the induction of fos, jun, and myc by EGF and TPA was not significantly inhibited in this cell line. An effect of p21(Asn-17) on fos induction was, however, demonstrated in transient expression assays in which quiescent NIH 3T3 cells were cotransfected with a fos-cat receptor plasmid plus a Ha-ras Asn-17 expression vector. In this assay, p21(Asn-17) inhibited chloramphenicol acetyltransferase expression induced by EGF and other growth factors. In contrast to its effect on DNA synthesis, however, Ha-ras Asn-17 expression did not inhibit fos-cat expression induced by TPA. Conversely, downregulation of protein kinase C did not inhibit fos-cat induction by activated ras or other oncogenes. These results suggest that ras proteins are involved in at least two parallel mitogenic signal transduction pathways, one of which is independent of protein kinase C. Although either pathway alone appears to be sufficient to induce fos, both appear to be necessary to induce the full mitogenic response.

scholarly journals Effect of a dominant inhibitory Ha-ras mutation on mitogenic signal transduction in NIH 3T3 cells.

1990 ◽  
Vol 10 (10) ◽  
pp. 5314-5323 ◽  
Author(s):  
H Cai ◽  
J Szeberényi ◽  
G M Cooper
Keyword(s):  
Signal Transduction ◽  
Protein Kinase C ◽  
Growth Factor ◽  
Protein Kinase ◽  
Dna Synthesis ◽  
3T3 Cells ◽  
Kinase C ◽  
Mitogenic Signal Transduction ◽  
Nih 3T3 ◽  
Mitogenic Signal

We used a dominant inhibitory mutation of c-Ha-ras which changes Ser-17 to Asn-17 in the gene product p21 [p21(Asn-17)Ha-ras] to investigate ras function in mitogenic signal transduction. An NIH 3T3 cell line [NIH(M17)] was isolated that displayed inducible expression of the mutant Ha-ras gene (Ha-ras Asn-17) via the mouse mammary tumor virus long terminal repeat and was growth inhibited by dexamethasone. The effect of dexamethasone induction on response of quiescent NIH(M17) cells to mitogens was then analyzed. Stimulation of DNA synthesis by epidermal growth factor (EGF) and 12-O-tetradecanoylphorbol-13-acetate (TPA) was completely blocked by p21(Asn-17) expression, and stimulation by serum, fibroblast growth factor, and platelet-derived growth factor was partially inhibited. However, the induction of fos, jun, and myc by EGF and TPA was not significantly inhibited in this cell line. An effect of p21(Asn-17) on fos induction was, however, demonstrated in transient expression assays in which quiescent NIH 3T3 cells were cotransfected with a fos-cat receptor plasmid plus a Ha-ras Asn-17 expression vector. In this assay, p21(Asn-17) inhibited chloramphenicol acetyltransferase expression induced by EGF and other growth factors. In contrast to its effect on DNA synthesis, however, Ha-ras Asn-17 expression did not inhibit fos-cat expression induced by TPA. Conversely, downregulation of protein kinase C did not inhibit fos-cat induction by activated ras or other oncogenes. These results suggest that ras proteins are involved in at least two parallel mitogenic signal transduction pathways, one of which is independent of protein kinase C. Although either pathway alone appears to be sufficient to induce fos, both appear to be necessary to induce the full mitogenic response.

Hydrolysis of phosphatidylcholine is stimulated by Ras proteins during mitogenic signal transduction

1992 ◽  
Vol 12 (12) ◽  
pp. 5329-5335
Author(s):  
H Cai ◽  
P Erhardt ◽  
J Szeberényi ◽  
M T Diaz-Meco ◽  
T Johansen ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Cell Proliferation ◽  
Growth Factor ◽  
Phorbol Esters ◽  
Ras Proteins ◽  
Mitogenic Signal Transduction ◽  
Nih 3T3 ◽  
Hydrolysis Of ◽  
Mitogenic Signal ◽  
Mitogenic Signals

We have used a dominant inhibitory ras mutant (Ha-ras Asn-17) to investigate the relationship of Ras proteins to hydrolysis of phosphatidylcholine (PC) in the transduction of mitogenic signals. Expression of Ha-Ras Asn-17 inhibited NIH 3T3 cell proliferation induced by polypeptide growth factors or phorbol esters. In contrast, the mitogenic activity of PC-specific phospholipase C (PC-PLC) was not inhibited by Ha-Ras Asn-17 expression. Similarly, cotransfection with a cloned PC-PLC gene bypassed the block to NIH 3T3 cell proliferation resulting from expression of the inhibitory ras mutant. Hydrolysis of PC can therefore induce cell proliferation in the absence of normal Ras activity, suggesting that PC-derived second messengers may act downstream of Ras in mitogenic signal transduction. This was substantiated by the finding that Ha-Ras Asn-17 expression inhibited growth factor-stimulated hydrolysis of PC. Taken together, these results indicate that PC hydrolysis is a target of Ras during the transduction of growth factor-initiated mitogenic signals.

scholarly journals Hydrolysis of phosphatidylcholine is stimulated by Ras proteins during mitogenic signal transduction.

1992 ◽  
Vol 12 (12) ◽  
pp. 5329-5335 ◽  
Author(s):  
H Cai ◽  
P Erhardt ◽  
J Szeberényi ◽  
M T Diaz-Meco ◽  
T Johansen ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Cell Proliferation ◽  
Growth Factor ◽  
Phorbol Esters ◽  
Ras Proteins ◽  
Mitogenic Signal Transduction ◽  
Nih 3T3 ◽  
Hydrolysis Of ◽  
Mitogenic Signal ◽  
Mitogenic Signals

We have used a dominant inhibitory ras mutant (Ha-ras Asn-17) to investigate the relationship of Ras proteins to hydrolysis of phosphatidylcholine (PC) in the transduction of mitogenic signals. Expression of Ha-Ras Asn-17 inhibited NIH 3T3 cell proliferation induced by polypeptide growth factors or phorbol esters. In contrast, the mitogenic activity of PC-specific phospholipase C (PC-PLC) was not inhibited by Ha-Ras Asn-17 expression. Similarly, cotransfection with a cloned PC-PLC gene bypassed the block to NIH 3T3 cell proliferation resulting from expression of the inhibitory ras mutant. Hydrolysis of PC can therefore induce cell proliferation in the absence of normal Ras activity, suggesting that PC-derived second messengers may act downstream of Ras in mitogenic signal transduction. This was substantiated by the finding that Ha-Ras Asn-17 expression inhibited growth factor-stimulated hydrolysis of PC. Taken together, these results indicate that PC hydrolysis is a target of Ras during the transduction of growth factor-initiated mitogenic signals.

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