Phospholipase C-mediated hydrolysis of phosphatidylcholine is a target of transforming growth factor beta 1 inhibitory signals

1992 ◽  
Vol 12 (1) ◽  
pp. 302-308
Author(s):  
M T Diaz-Meco ◽  
I Dominguez ◽  
L Sanz ◽  
M M Municio ◽  
E Berra ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Growth ◽  
Phospholipase C ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Tgf Beta ◽  
Transduction Mechanisms ◽  
Growth Factor Beta ◽  
Mitogenic Signal Transduction ◽  
Hydrolysis Of

Cell growth and tumor transformation can be restrained in certain cell systems by the action of transforming growth factor beta (TGF-beta). It has been established that the mechanism whereby TGF-beta 1 inhibits cell growth does not interfere with the triggering of early mitogenic signal transduction mechanisms. Phospholipase C-catalyzed hydrolysis of phosphatidylcholine (PC) is a relatively late step in the cascade activated by growth factors. Therefore, conceivably activation of phospholipase C-catalyzed hydrolysis of PC could be the target of TGF-beta 1 action. In the study reported here, we demonstrate that TGF-beta 1 inhibits the coupling of ras p21 to the activation of PC hydrolysis, which appears to be critical for the antiproliferative effects of TGF-beta 1.

scholarly journals Phospholipase C-mediated hydrolysis of phosphatidylcholine is a target of transforming growth factor beta 1 inhibitory signals.

1992 ◽  
Vol 12 (1) ◽  
pp. 302-308 ◽  
Author(s):  
M T Diaz-Meco ◽  
I Dominguez ◽  
L Sanz ◽  
M M Municio ◽  
E Berra ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Growth ◽  
Phospholipase C ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Tgf Beta ◽  
Transduction Mechanisms ◽  
Growth Factor Beta ◽  
Mitogenic Signal Transduction ◽  
Hydrolysis Of

Cell growth and tumor transformation can be restrained in certain cell systems by the action of transforming growth factor beta (TGF-beta). It has been established that the mechanism whereby TGF-beta 1 inhibits cell growth does not interfere with the triggering of early mitogenic signal transduction mechanisms. Phospholipase C-catalyzed hydrolysis of phosphatidylcholine (PC) is a relatively late step in the cascade activated by growth factors. Therefore, conceivably activation of phospholipase C-catalyzed hydrolysis of PC could be the target of TGF-beta 1 action. In the study reported here, we demonstrate that TGF-beta 1 inhibits the coupling of ras p21 to the activation of PC hydrolysis, which appears to be critical for the antiproliferative effects of TGF-beta 1.

scholarly journals Transforming growth factor beta 1 selectively regulates early murine hematopoietic progenitors and inhibits the growth of IL-3-dependent myeloid leukemia cell lines.

1988 ◽  
Vol 168 (2) ◽  
pp. 737-750 ◽  
Author(s):  
J R Keller ◽  
C Mantel ◽  
G K Sing ◽  
L R Ellingsworth ◽  
S K Ruscetti ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Growth Factor ◽  
Cell Growth ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Potent Inhibitor ◽  
Leukemia Cell ◽  
Leukemic Cell ◽  
Tgf Beta ◽  
Growth Factor Beta

Transforming growth factor beta 1 (TGF-beta 1) has been shown to be associated with active centers of hematopoiesis and lymphopoiesis in the developing fetus. Therefore, the effects of TGF-beta 1 on mouse hematopoiesis were studied. TGF-beta 1 is a potent inhibitor of IL-3-induced bone marrow proliferation, but it does not inhibit the proliferation induced by granulocyte/macrophage, colony-stimulating factor (CSF), granulocyte CSF, and erythropoietin (Epo). TGF-beta 1 also inhibits IL-3-induced multipotential colony formation of bone marrow cells in soft agar, which includes early erythroid differentiation, while Epo-induced terminal differentiation is unaffected. In addition, IL-3-induced granulocyte/macrophage colonies were inhibited; however, small clusters of differentiated myeloid cells were consistently seen in cultures containing IL-3 and TGF-beta 1. Thus, TGF-beta 1 selectively inhibits early hematopoietic progenitor growth and differentiation but not more mature progenitors. TGF-beta 1 is also a potent inhibitor of IL-3-dependent and -independent myelomonocytic leukemic cell growth, while the more mature erythroid and macrophage leukemias are insensitive. Therefore, TGF-beta 1 functions as a selective regulator of differentiating normal hematopoietic cells, and suppresses myeloid leukemic cell growth.

scholarly journals Basic fibroblast growth factor counteracts the suppressive effect of transforming growth factor-beta 1 on human myeloid progenitor cells

Blood ◽  
1993 ◽  
Vol 81 (4) ◽  
pp. 909-915 ◽  
Author(s):  
JL Gabrilove ◽  
G Wong ◽  
E Bollenbacher ◽  
K White ◽  
S Kojima ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Growth Factor ◽  
Cell Growth ◽  
Transforming Growth Factor Beta ◽  
Progenitor Cell ◽  
Transforming Growth Factor ◽  
Fibroblast Growth ◽  
Tgf Beta ◽  
Gm Csf ◽  
Growth Factor Beta

Abstract We have previously shown that basic fibroblast growth factor (bFGF) is mitogenic for human bone marrow stromal cells and enhances myelopoiesis in human long-term bone marrow culture. In the present study, we examined the mechanism by which bFGF enhances granulopoiesis. We observed that bFGF significantly abrogated the inhibitory effect of transforming growth factor-beta 1 (TGF-beta 1) on granulocyte- macrophage colony-stimulating factor (GM-CSF)-supported progenitor cell growth (P = .009). The partial reversal of TGF-beta 1-mediated suppression was dependent on the dose of bFGF used. In addition, we noted that the inclusion of neutralizing antibody to TGF-beta 1 significantly augmented the clonogenic response to GM-CSF. We have also shown that 10 ng/mL or 100 ng/mL of bFGF resulted in a 30% to 100% increase in GM-CSF-mediated progenitor cell growth (P = .0001). These data suggest that bFGF may enhance myelopoiesis by modulating the inhibitory response to TGF-beta 1.

scholarly journals Basic fibroblast growth factor counteracts the suppressive effect of transforming growth factor-beta 1 on human myeloid progenitor cells

Blood ◽  
1993 ◽  
Vol 81 (4) ◽  
pp. 909-915
Author(s):  
JL Gabrilove ◽  
G Wong ◽  
E Bollenbacher ◽  
K White ◽  
S Kojima ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Growth Factor ◽  
Cell Growth ◽  
Transforming Growth Factor Beta ◽  
Progenitor Cell ◽  
Transforming Growth Factor ◽  
Fibroblast Growth ◽  
Tgf Beta ◽  
Gm Csf ◽  
Growth Factor Beta

We have previously shown that basic fibroblast growth factor (bFGF) is mitogenic for human bone marrow stromal cells and enhances myelopoiesis in human long-term bone marrow culture. In the present study, we examined the mechanism by which bFGF enhances granulopoiesis. We observed that bFGF significantly abrogated the inhibitory effect of transforming growth factor-beta 1 (TGF-beta 1) on granulocyte- macrophage colony-stimulating factor (GM-CSF)-supported progenitor cell growth (P = .009). The partial reversal of TGF-beta 1-mediated suppression was dependent on the dose of bFGF used. In addition, we noted that the inclusion of neutralizing antibody to TGF-beta 1 significantly augmented the clonogenic response to GM-CSF. We have also shown that 10 ng/mL or 100 ng/mL of bFGF resulted in a 30% to 100% increase in GM-CSF-mediated progenitor cell growth (P = .0001). These data suggest that bFGF may enhance myelopoiesis by modulating the inhibitory response to TGF-beta 1.

scholarly journals Early human thymocyte proliferation is regulated by an externally controlled autocrine transforming growth factor-beta 1 mechanism

Blood ◽  
1995 ◽  
Vol 85 (12) ◽  
pp. 3594-3601 ◽  
Author(s):  
MD Mossalayi ◽  
F Mentz ◽  
F Ouaaz ◽  
AH Dalloul ◽  
C Blanc ◽  
...  
Keyword(s):  
T Cell ◽  
Growth Factor ◽  
Cell Growth ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Cellular Interactions ◽  
Tgf Beta ◽  
Growth Responses ◽  
Cd8 Cell ◽  
Growth Factor Beta

Early thymocytes undergo extensive proliferation after their entry into the thymus, but cellular interactions and cytokines regulating this intrathymic step remain to be determined. We analyzed the effects of various T-cell growth factors and cellular interactions on in vitro proliferation of early CD2+CD3/TCR-CD4-CD8-(triple negative [TN]) human thymocytes. Freshly isolated TN cells were then assayed for their growth capacity after incubation with CD2I+III-monoclonal antibody (MoAb), recombinant human interleukin-2 (IL-2), IL-7, and/or IL-4. These cells displayed significant proliferative responses with IL-4, IL-7, or CD2-MoAb+IL-2. The addition of recombinant transforming growth factor beta (TGF beta) or autologous irradiated CD3+CD8+CD4- cells to TN cell cultures dramatically decreased their growth responses to IL-2 and IL-7, whereas IL-4-induced proliferation was less sensitive to growth inhibition. We thus asked whether the CD8+ cell-derived inhibitory effect was due to TGF beta. The addition of neutralizing anti-TGF beta MoAb completely abolished CD8+ cell-derived inhibition of TN cell growth. Analysis of CD8+ cell-derived supernatants indicated that these cells had low TGF beta 1 production capacity, whereas TN cells secrete significantly high levels of TGF beta 1. Cell fixation studies showed that TN cells were the source of the TGF beta. TGF beta 1 released from TN cells was in the latent form that became the active inhibitory form through interaction of TN cells with CD8+ cells. Together, these data suggest a role for TGF beta 1 as an externally controlled, autocrine inhibitory factor for human early thymocytes, with a regulatory role in thymic T-cell output.

scholarly journals Identification of a novel transforming growth factor-beta (TGF-beta 5) mRNA in Xenopus laevis.

1990 ◽  
Vol 265 (2) ◽  
pp. 1089-1093 ◽  
Author(s):  
P Kondaiah ◽  
M J Sands ◽  
J M Smith ◽  
A Fields ◽  
A B Roberts ◽  
...  
Keyword(s):  
Growth Factor ◽  
Xenopus Laevis ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Tgf Beta ◽  
Growth Factor Beta

scholarly journals Recombinant type 1 transforming growth factor beta precursor produced in Chinese hamster ovary cells is glycosylated and phosphorylated.

1988 ◽  
Vol 8 (5) ◽  
pp. 2229-2232 ◽  
Author(s):  
A M Brunner ◽  
L E Gentry ◽  
J A Cooper ◽  
A F Purchio
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Chinese Hamster Ovary ◽  
Transforming Growth Factor ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Tgf Beta ◽  
Ovary Cells ◽  
Growth Factor Beta

Analyses of cDNA clones coding for simian type 1 transforming growth factor beta (TGF-beta 1) suggest that there are three potential sites for N-linked glycosylation located in the amino terminus of the precursor region. Analysis of [3H]glucosamine-labeled serum-free supernatants from a line of Chinese hamster ovary cells which secrete high levels of recombinant TGF-beta 1 indicate that the TGF-beta 1 precursor, but not the mature form, is glycosylated. Digestion with neuraminidase resulted in a shift in migration of the two TGF-beta 1 precursor bands, which suggests that they contain sialic acid residues. Endoglycosidase H had no noticeable effect. Treatment with N-glycanase produced two faster-migrating sharp bands, the largest of which had a molecular weight of 39 kilodaltons. TGF-beta 1-specific transcripts produced by SP6 polymerase programmed the synthesis of a 42-kilodalton polypeptide which, we suggest, is the unmodified protein backbone of the precursor. Labeling with 32Pi showed that the TGF-beta 1 precursor was phosphorylated in the amino portion of the molecule.

Sign in / Sign up

Export Citation Format

Share Document