The Suppression of Small GTPase Rho Signal Transduction Pathway Inhibits Angiogenesis in Vitro and in Vivo

2000 ◽  
Vol 269 (2) ◽  
pp. 633-640 ◽  
Author(s):  
Shigeki Uchida ◽  
Go Watanabe ◽  
Yutaka Shimada ◽  
Masato Maeda ◽  
Atsushi Kawabe ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Signal Transduction Pathway ◽  
Small Gtpase ◽  
Transduction Pathway

Novel pathway for thyroid hormone receptor action through interaction with jun and fos oncogene activities

1991 ◽  
Vol 11 (12) ◽  
pp. 6016-6025
Author(s):  
X K Zhang ◽  
K N Wills ◽  
M Husmann ◽  
T Hermann ◽  
M Pfahl
Keyword(s):  
Signal Transduction ◽  
Dna Binding ◽  
Thyroid Hormone Receptor ◽  
Gene Activation ◽  
Signal Transduction Pathway ◽  
Large Family ◽  
Transduction Pathway ◽  
Regulatory Pathway

Many essential biological pathways, including cell growth, development, and metabolism, are regulated by thyroid hormones (THs). TH action is mediated by intracellular receptors that belong to a large family of ligand-dependent transcription factors, including the steroid hormone and retinoic acid receptors. So far it has been assumed that TH receptors (TRs) regulate gene transcription only through the classical protein-DNA interaction mechanism. Here we provide evidence for a regulatory pathway that allows cross-talk between TRs and the signal transduction pathway used by many growth factors, oncogenes, and tumor promoters. In transient transfection studies, we observed that the oncogenes c-jun and c-fos inhibit TR activities, while TRs inhibit induction of the c-fos promoter and repress AP-1 site-dependent gene activation. A truncated TR that lacks only 17 amino acids from the carboxy terminus can no longer antagonize AP-1 activity. The cross-regulation between TRs and the signal transduction pathway appears to be based on the ability of TRs to inhibit DNA binding of the transcription factor AP-1 in the presence of THs. The constituents of AP-1, c-Jun, and c-Fos, vice versa, can inhibit TR-induced gene activation in vivo, and c-Jun inhibits TR DNA binding in vitro. This novel regulatory pathway is likely to play a major role in growth control and differentiation by THs.

scholarly journals Erythropoietin-Induced Activation of STAT5 Is Impaired in the Myelodysplastic Syndrome

Blood ◽  
1997 ◽  
Vol 89 (5) ◽  
pp. 1690-1700 ◽  
Author(s):  
Lies H. Hoefsloot ◽  
Martine P. van Amelsvoort ◽  
Lianne C.A.M. Broeders ◽  
Dorien C. van der Plas ◽  
Kirsten van Lom ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Myelodysplastic Syndrome ◽  
Signal Transduction Pathway ◽  
Binding Activity ◽  
Signal Transducer ◽  
Transduction Pathway ◽  
Normal Bone ◽  
Marrow Cells

Abstract Patients with myelodysplastic syndrome (MDS) have ineffective in vivo and in vitro erythropoiesis, characterized by an impaired response to erythropoietin (Epo). We examined proliferation and maturation of MDS marrow cells in response to Epo in more detail. Epo-dependent DNA synthesis as well as induction of GATA-1 binding activity in marrow cells from 15 MDS cases were severely reduced as compared with normal bone marrow (NBM). Additionally, the appearance of morphologically identifiable erythroid cells was decreased in MDS cell cultures. These data indicate that both the Epo-dependent proliferation as well as the differentiation induction by Epo is suppressed. To study more upstream events of the Epo signal transduction route we investigated activation of the signal transducer and activator of transcription (STAT) 5. In all 15 MDS samples tested, STAT5 activation was absent or greatly suppressed in response to Epo. In contrast, interleukin-3 induced a normal STAT5 response in MDS cells. Further, in MDS the subset of CD71+ BM cells that is phenotypically similar to Epo-responsive cells in normal marrow, was present. We conclude that the Epo response in MDS is disturbed at an early point in the Epo receptor (EpoR) signal transduction pathway.

scholarly journals Erythropoietin-Induced Activation of STAT5 Is Impaired in the Myelodysplastic Syndrome

Blood ◽  
1997 ◽  
Vol 89 (5) ◽  
pp. 1690-1700 ◽  
Author(s):  
Lies H. Hoefsloot ◽  
Martine P. van Amelsvoort ◽  
Lianne C.A.M. Broeders ◽  
Dorien C. van der Plas ◽  
Kirsten van Lom ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Myelodysplastic Syndrome ◽  
Signal Transduction Pathway ◽  
Binding Activity ◽  
Signal Transducer ◽  
Transduction Pathway ◽  
Normal Bone ◽  
Marrow Cells

Patients with myelodysplastic syndrome (MDS) have ineffective in vivo and in vitro erythropoiesis, characterized by an impaired response to erythropoietin (Epo). We examined proliferation and maturation of MDS marrow cells in response to Epo in more detail. Epo-dependent DNA synthesis as well as induction of GATA-1 binding activity in marrow cells from 15 MDS cases were severely reduced as compared with normal bone marrow (NBM). Additionally, the appearance of morphologically identifiable erythroid cells was decreased in MDS cell cultures. These data indicate that both the Epo-dependent proliferation as well as the differentiation induction by Epo is suppressed. To study more upstream events of the Epo signal transduction route we investigated activation of the signal transducer and activator of transcription (STAT) 5. In all 15 MDS samples tested, STAT5 activation was absent or greatly suppressed in response to Epo. In contrast, interleukin-3 induced a normal STAT5 response in MDS cells. Further, in MDS the subset of CD71+ BM cells that is phenotypically similar to Epo-responsive cells in normal marrow, was present. We conclude that the Epo response in MDS is disturbed at an early point in the Epo receptor (EpoR) signal transduction pathway.

Induction of phosphoinositide-mediated signal transduction pathway by 17 beta-oestradiol in rat vaginal epithelial cells

1997 ◽  
Vol 19 (3) ◽  
pp. 249-257 ◽  
Author(s):  
S Singh ◽  
PD Gupta
Keyword(s):  
Signal Transduction ◽  
Epithelial Cells ◽  
Calcium Uptake ◽  
Inositol Phosphate ◽  
Primary Cultures ◽  
Signal Transduction Pathway ◽  
Transduction Pathway ◽  
Vaginal Epithelial Cells

In the present study, the induction of the phosphoinositide signal transduction pathway by 17 beta-oestradiol has been demonstrated in rat vaginal epithelial cells (VEC). We have shown an increase in the metabolism of phosphoinositol lipids by 3H-myoinositol incorporation as well as production of inositol phosphate in VEC in vivo and in vitro following oestradiol administration. Concomitant changes in intracellular calcium levels have also been observed under the influence of oestradiol. To rule out the effects of cytokines, parallel studies were performed using primary cultures of VEC. Oestradiol-induced calcium uptake was seen even in the presence of actinomycin D and cycloheximide which inhibit transcription and translation respectively. Calcium uptake was blocked by neomycin, an inhibitor of phosphoinositol lipid metabolism, and by the oestrogen receptor antagonist tamoxifen. Results suggest that oestradiol induces second messenger pathways in the VEC through specific receptors. Implications of these observations in cellular differentiation processes are discussed.

scholarly journals Novel pathway for thyroid hormone receptor action through interaction with jun and fos oncogene activities.

1991 ◽  
Vol 11 (12) ◽  
pp. 6016-6025 ◽  
Author(s):  
X K Zhang ◽  
K N Wills ◽  
M Husmann ◽  
T Hermann ◽  
M Pfahl
Keyword(s):  
Signal Transduction ◽  
Dna Binding ◽  
Thyroid Hormone Receptor ◽  
Gene Activation ◽  
Signal Transduction Pathway ◽  
Large Family ◽  
Transduction Pathway ◽  
Regulatory Pathway

Many essential biological pathways, including cell growth, development, and metabolism, are regulated by thyroid hormones (THs). TH action is mediated by intracellular receptors that belong to a large family of ligand-dependent transcription factors, including the steroid hormone and retinoic acid receptors. So far it has been assumed that TH receptors (TRs) regulate gene transcription only through the classical protein-DNA interaction mechanism. Here we provide evidence for a regulatory pathway that allows cross-talk between TRs and the signal transduction pathway used by many growth factors, oncogenes, and tumor promoters. In transient transfection studies, we observed that the oncogenes c-jun and c-fos inhibit TR activities, while TRs inhibit induction of the c-fos promoter and repress AP-1 site-dependent gene activation. A truncated TR that lacks only 17 amino acids from the carboxy terminus can no longer antagonize AP-1 activity. The cross-regulation between TRs and the signal transduction pathway appears to be based on the ability of TRs to inhibit DNA binding of the transcription factor AP-1 in the presence of THs. The constituents of AP-1, c-Jun, and c-Fos, vice versa, can inhibit TR-induced gene activation in vivo, and c-Jun inhibits TR DNA binding in vitro. This novel regulatory pathway is likely to play a major role in growth control and differentiation by THs.

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