Inadequacy of the Janus Kinase 2/Signal Transducer and Activator of Transcription Signal Transduction Pathway to Mediate Episodic Growth Hormone-Dependent Regulation of Hepatic CYP2C11

2004 ◽  
Vol 67 (3) ◽  
pp. 891-901 ◽  
Author(s):  
Ashish S. Verma ◽  
Ravindra N. Dhir ◽  
Bernard H. Shapiro
Keyword(s):  
Signal Transduction ◽  
Growth Hormone ◽  
Signal Transduction Pathway ◽  
Janus Kinase ◽  
Signal Transducer ◽  
Transduction Pathway ◽  
Janus Kinase 2 ◽  
Episodic Growth

scholarly journals Effects of Chronic Ethanol on Hepatic and Renal CYP2C11 in the Male Rat: Interactions with the Janus-Kinase 2-Signal Transducer and Activators of Transcription Proteins 5b Pathway

Endocrinology ◽  
2003 ◽  
Vol 144 (9) ◽  
pp. 3969-3976 ◽  
Author(s):  
T. M. Badger ◽  
M. J. J. Ronis ◽  
S. J. Frank ◽  
Y. Chen ◽  
L. He
Keyword(s):  
Signal Transduction ◽  
Signal Transduction Pathway ◽  
Serum Testosterone ◽  
Janus Kinase ◽  
Chronic Ethanol ◽  
Male Rats ◽  
Male Rat ◽  
Signal Transducer ◽  
Transduction Pathway

Abstract Chronic alcohol intake in male rats results in: 1) demasculinization of the GH pulse pattern; 2) reduced serum testosterone concentrations; and 3) decreased expression hepatic CYP2C11. Hepatic CYP2C11 expression is regulated by the male pattern of GH through the Janus-kinase/signal transducer and activators of transcription proteins (JAK/STAT) signal transduction pathway in the male rat. Renal CYP2C11 is regulated by testosterone, not GH. The involvement of the JAK/STAT5b signal transduction pathway in renal CYP2C11 signaling has not been studied. We tested the hypothesis that ethanol reduces CYP2C11 levels by interfering with the JAK/STAT5b pathway. Using a total enteral nutrition (TEN) model to feed rats a well-balanced diet, we have studied the effects of chronic ethanol intake (21 d) on hepatic and renal JAK/STAT pathway of adult male rats (8–10/group). We found decreased hepatic and renal expression of CYP2C11 in ethanol-fed rats with concomitant decreases in STAT5b and phospho-STAT5b, decreased in vitro hepatic STAT5b binding to a CYP2C11 promoter element and no effects on hepatic GHR levels. Ethanol caused tissue specific effects in phospho-JAK2 and JAK2, with increased levels in the liver, but decreased JAK2 expression in the kidney. We conclude that ethanol suppression of CYP2C11 expression is clearly associated with reductions in STAT5b levels, but not necessarily in reductions of JAK2 levels. The mechanisms underlying ethanol-induced suppression of STAT5b is yet to be determined, as is the question of whether this is secondary to hormonal effects or a direct ethanol effect.

scholarly journals Signal Transducer and Activator of Transcription (Stat)-Induced Stat Inhibitor 1 (Ssi-1)/Suppressor of Cytokine Signaling 1 (Socs1) Inhibits Insulin Signal Transduction Pathway through Modulating Insulin Receptor Substrate 1 (Irs-1) Phosphorylation

2001 ◽  
Vol 193 (2) ◽  
pp. 263-270 ◽  
Author(s):  
Yoshinori Kawazoe ◽  
Tetsuji Naka ◽  
Minoru Fujimoto ◽  
Hidetsugu Kohzaki ◽  
Yoshiaki Morita ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Negative Feedback ◽  
Signal Transduction Pathway ◽  
Cytokine Signaling ◽  
Insulin Receptor Substrate ◽  
Signal Transducer ◽  
Transduction Pathway ◽  
Insulin Signal Transduction ◽  
Insulin Signal ◽  
Insulin Signal Transduction Pathway

Signal transducer and activator of transcription (STAT)-induced STAT inhibitor 1 (SSI-1) is known to function as a negative feedback regulator of cytokine signaling, but it is unclear whether it is involved in other biological events. Here, we show that SSI-1 participates and plays an important role in the insulin signal transduction pathway. SSI-1–deficient mice showed a significantly low level of blood sugar. While the forced expression of SSI-1 reduced the phosphorylation level of insulin receptor substrate 1 (IRS-1), SSI-1 deficiency resulted in sustained phosphorylation of IRS-1 in response to insulin. Furthermore, SSI-1 achieves this inhibition both by binding directly to IRS-1 and by suppressing Janus kinases. These findings suggest that SSI-1 acts as a negative feedback factor also in the insulin signal transduction pathway through the suppression of IRS-1 phosphorylation.

scholarly journals Molecular interactions of EphA4, growth hormone receptor, Janus kinase 2, and signal transducer and activator of transcription 5B

PLoS ONE ◽  
2017 ◽  
Vol 12 (7) ◽  
pp. e0180785 ◽  
Author(s):  
Takahiro Sawada ◽  
Daiki Arai ◽  
Xuefeng Jing ◽  
Masayasu Miyajima ◽  
Stuart J. Frank ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Molecular Interactions ◽  
Hormone Receptor ◽  
Growth Hormone Receptor ◽  
Janus Kinase ◽  
Signal Transducer ◽  
Janus Kinase 2

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.

Participation of JAK, STAT and unknown proteins in human placental lactogen-induced signaling: a unique signaling pathway different from prolactin and growth hormone

1997 ◽  
Vol 153 (1) ◽  
pp. R1-R3 ◽  
Author(s):  
Takashi Takeda ◽  
Hirohisa Kurachi ◽  
Toshiya Yamamoto ◽  
Hiroaki Homma ◽  
Kenichirou Morishige ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Growth Hormone ◽  
Signal Transduction Pathway ◽  
Human Growth ◽  
Placental Lactogen ◽  
Human Placental Lactogen ◽  
Signal Transducer ◽  
Stat Proteins ◽  
Unique Signal ◽  
Stat Pathway

Abstract The signal transduction mechanism involved in human placental lactogen (hPL) was studied. We have identified that hPL rapidly stimulated the tyrosine phosphorylation of at least 7 proteins including Janus Kinases (JAK1 and JAK2) and a signal transducer and activator of transcription protein (Stat3). This is the first evidence that the JAK-STAT pathway is involved in the hPL signaling. Moreover, two unknown proteins which were different from STAT proteins (Stat1, 3 and 5) in sizes were predominantly tyrosine-phosphorylated. Because human growth hormone (hGH) activates Stat1, 3, 5 and human prolactin (hPRL) activates Stat5, these results show that hPL uses a unique signal transduction pathway which is different from hGH and hPRL.

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.

Downregulation of the growth hormone-induced Janus kinase 2/signal transducer and activator of transcription 5 signaling pathway requires an intact actin cytoskeleton

2004 ◽  
Vol 294 (1) ◽  
pp. 269-280 ◽  
Author(s):  
Elizabeth Rico-Bautista ◽  
Ciro Negrı́n-Martı́nez ◽  
Javier Novoa-Mogollón ◽  
Leandro Fernández-Perez ◽  
Amilcar Flores-Morales
Keyword(s):  
Growth Hormone ◽  
Actin Cytoskeleton ◽  
Signaling Pathway ◽  
Janus Kinase ◽  
Signal Transducer ◽  
Janus Kinase 2
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