Role of a Janus kinase 2-dependent signaling pathway in platelet activation

The Janus kinase (JAK) signal transducer and activator of transcription (STAT) signaling pathway serves as an important downstream mediator for a variety of cytokines, hormones, and growth factors. Emerging evidence suggests JAK/STAT signaling pathway plays an important role in bone development, metabolism, and healing. In this light, pro-inflammatory cytokines are now clearly implicated in these processes as they can perturb normal bone remodeling through their action on osteoclasts and osteoblasts at both intra- and extra-articular skeletal sites. Here, we summarize the role of JAK/STAT pathway on development, homeostasis, and regeneration based on skeletal phenotype of individual JAK and STAT gene knockout models and selective inhibition of components of the JAK/STAT signaling including influences of JAK inhibition in osteoclasts, osteoblasts, and osteocytes.

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Multi-Factor Regulation of the Master Modulator LeuO for the Cyclic-(Phe-Pro) Signaling Pathway in Vibrio vulnificus

Scientific Reports ◽

10.1038/s41598-019-56855-4 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Na-Young Park ◽

In Hwang Kim ◽

Yancheng Wen ◽

Keun-Woo Lee ◽

Sora Lee ◽

...

Keyword(s):

Rna Polymerase ◽

Signaling Pathway ◽

Vibrio Vulnificus ◽

Dna Bending ◽

Titration Calorimetry ◽

Master Regulator ◽

Bending Mechanism ◽

Periplasmic Domain ◽

Dependent Signaling Pathway

AbstractLeuO plays the role of a master regulator in the cyclic-L-phenylalanine-L-proline (cFP)-dependent signaling pathway in Vibrio vulnificus. cFP, as shown through isothermal titration calorimetry analysis, binds specifically to the periplasmic domain of ToxR. Binding of cFP triggers a change in the cytoplasmic domain of ToxR, which then activates transcription of leuO encoding a LysR-type regulator. LeuO binds to the region upstream of its own coding sequence, inhibiting its own transcription and maintaining a controlled level of expression. A five-bp deletion in this region abolished expression of LeuO, but a ten-bp deletion did not, suggesting that a DNA bending mechanism is involved in the regulation. Furthermore, binding of RNA polymerase was significantly lower both in the deletion of the ToxR binding site and in the five-bp deletion, but not in the ten-bp deletion, as shown in pull-down assays using an antibody against RNA polymerase subunit α. In summary, multiple factors are involved in control of the expression of LeuO, a master regulator that orchestrates downstream regulators to modulate factors required for survival and pathogenicity of the pathogen.

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Non-coding RNA 886 promotes renal cell carcinoma growth and metastasis through the Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway

Molecular Medicine Reports ◽

10.3892/mmr.2017.7093 ◽

2017 ◽

Vol 16 (4) ◽

pp. 4273-4278 ◽

Cited By ~ 2

Author(s):

Jun Lei ◽

Ju-Hua Xiao ◽

Shou-Hua Zhang ◽

Zhi-Qiang Liu ◽

Kai Huang ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Signaling Pathway ◽

Renal Cell ◽

Janus Kinase ◽

Signal Transducer ◽

Janus Kinase 2 ◽

Non Coding Rna ◽

Transcription 3

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Role of a JAK3-dependent Biochemical Signaling Pathway in Platelet Activation and Aggregation

Journal of Biological Chemistry ◽

10.1074/jbc.m011405200 ◽

2001 ◽

Vol 276 (21) ◽

pp. 17815-17822 ◽

Cited By ~ 34

Author(s):

Heather E. Tibbles ◽

Alexei Vassilev ◽

Heather Wendorf ◽

Dawn Schonhoff ◽

Dan Zhu ◽

...

Keyword(s):

Signaling Pathway ◽

Platelet Activation

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Effects of dexmedetomidine postconditioning on myocardial ischemia and the role of the PI3K/Akt-dependent signaling pathway in reperfusion injury

Molecular Medicine Reports ◽

10.3892/mmr.2016.5345 ◽

2016 ◽

Vol 14 (1) ◽

pp. 797-803 ◽

Cited By ~ 27

Author(s):

XIANG YANG CHENG ◽

XIAO YU GU ◽

QIN GAO ◽

QIAO FENG ZONG ◽

XIAO HONG LI ◽

...

Keyword(s):

Myocardial Ischemia ◽

Reperfusion Injury ◽

Signaling Pathway ◽

Dependent Signaling Pathway

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Two Distinct Signaling Pathways Downstream of Janus Kinase 2 Play Redundant Roles for Antiapoptotic Activity of Granulocyte-Macrophage Colony-stimulating Factor

Molecular Biology of the Cell ◽

10.1091/mbc.10.11.3959 ◽

1999 ◽

Vol 10 (11) ◽

pp. 3959-3970 ◽

Cited By ~ 17

Author(s):

Rui Liu ◽

Tohru Itoh ◽

Ken-ichi Arai ◽

Sumiko Watanabe

Keyword(s):

Signaling Pathway ◽

Janus Kinase ◽

Janus Kinase 2 ◽

Colony Stimulating Factor ◽

Tyrosine Residues ◽

Gm Csf ◽

Macrophage Colony Stimulating Factor ◽

Antiapoptotic Activity ◽

Macrophage Colony ◽

Stimulating Factor

Human granulocyte-macrophage colony-stimulating factor (hGM-CSF) induces proliferation and sustains the viability of the mouse interleukin-3-dependent cell line BA/F3 expressing the hGM-CSF receptor. Analysis of the antiapoptosis activity of GM-CSF receptor βc mutants showed that box1 but not the C-terminal region containing tyrosine residues is essential for GM-CSF-dependent antiapoptotic activity. Because βc mutants, which activate Janus kinase 2 but neither signal transducer and activator of transcription 5 nor the MAPK cascade sustain antiapoptosis activity, involvement of Janus kinase 2, excluding the above molecules, in antiapoptosis activity seems likely. GM-CSF activates phosphoinositide-3-OH kinase as well as Akt, and activation of both was suppressed by addition of wortmannin. Interestingly, wortmannin did not affect GM-CSF-dependent antiapoptosis, thus indicating that the phosphoinositide-3-OH kinase pathway is not essential for cell surivival. Analysis using the tyrosine kinase inhibitor genistein and a MAPK/extracellular signal-regulated kinase (ERK) kinase 1 inhibitor, PD98059, indicates that activation of either the genistein-sensitive signaling pathway or the PD98059-sensitive signaling pathway from βc may be sufficient to suppress apoptosis. Wild-type and a βc mutant lacking tyrosine residues can induce expression of c-myc andbcl-xLgenes; however, drug sensitivities for activation of these genes differ from those for antiapoptosis activity of GM-CSF, which means that these gene products may be involved yet are inadequate to promote cell survival.

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