In vitro activation of murine peritoneal macrophages by ultraviolet B radiation: upregulation of CD18, production of NO, proinflammatory cytokines and a signal transduction 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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Far1 and Fus3 link the mating pheromone signal transduction pathway to three G1-phase Cdc28 kinase complexes

Molecular and Cellular Biology ◽

10.1128/mcb.13.9.5659-5669.1993 ◽

1993 ◽

Vol 13 (9) ◽

pp. 5659-5669 ◽

Cited By ~ 1

Author(s):

M Tyers ◽

B Futcher

Keyword(s):

Signal Transduction ◽

Protein Kinase ◽

Signal Transduction Pathway ◽

Mitogen Activated Protein Kinase ◽

G1 Phase ◽

Transduction Pathway ◽

Yeast Saccharomyces Cerevisiae ◽

Alpha Factor ◽

Mitogen Activated Protein

In the yeast Saccharomyces cerevisiae, the Cdc28 protein kinase controls commitment to cell division at Start, but no biologically relevant G1-phase substrates have been identified. We have studied the kinase complexes formed between Cdc28 and each of the G1 cyclins Cln1, Cln2, and Cln3. Each complex has a specific array of coprecipitated in vitro substrates. We identify one of these as Far1, a protein required for pheromone-induced arrest at Start. Treatment with alpha-factor induces a preferential association and/or phosphorylation of Far1 by the Cln1, Cln2, and Cln3 kinase complexes. This induced interaction depends upon the Fus3 protein kinase, a mitogen-activated protein kinase homolog that functions near the bottom of the alpha-factor signal transduction pathway. Thus, we trace a path through which a mitogen-activated protein kinase regulates a Cdc2 kinase.

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

Blood ◽

10.1182/blood.v89.5.1690 ◽

1997 ◽

Vol 89 (5) ◽

pp. 1690-1700 ◽

Cited By ~ 67

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.

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