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Related Concept Videos

Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Intracellular Signaling Cascades01:24

Intracellular Signaling Cascades

Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
Amplifying Signals via Second Messengers01:15

Amplifying Signals via Second Messengers

Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...

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Related Experiment Videos

Signaling pathways regulating IL-1alpha-induced COX-2 expression.

S Ogata1, Y Kubota, T Yamashiro

  • 1Department of Oral and Maxillofacial Surgery, Graduate School of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.

Journal of Dental Research
|January 26, 2007
PubMed
Summary

Interleukin-1alpha (IL-1alpha) activates cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) production in odontogenic keratocyst fibroblasts via protein kinase C (PKC) and mitogen-activated protein kinase pathways.

Related Experiment Videos

Area of Science:

  • Oral biology
  • Cell signaling
  • Molecular mechanisms

Background:

  • Odontogenic keratocysts are aggressive cystic tumors.
  • Interleukin-1alpha (IL-1alpha) is implicated in their pathogenesis.
  • Signaling pathways linking IL-1alpha to prostaglandin E2 (PGE2) production are not fully understood.

Purpose of the Study:

  • To investigate the signaling pathways by which IL-1alpha regulates cyclooxygenase-2 (COX-2) expression and PGE2 production in odontogenic keratocyst fibroblasts.

Main Methods:

  • Fibroblast cell culture
  • Quantitative PCR for COX-2 mRNA
  • Western blotting for protein expression
  • ELISA for PGE2 secretion
  • Inhibitor studies (PD-98059, SB-203580, SP-600125, PDTC, staurosporine)

Main Results:

  • IL-1alpha significantly increased COX-2 mRNA and protein expression, and PGE2 secretion.
  • IL-1alpha induced phosphorylation of ERK1/2, p38 MAPK, and JNK.
  • Inhibitors of ERK1/2, p38, JNK, and NF-kappaB attenuated IL-1alpha-induced COX-2 expression and PGE2 secretion.
  • Protein kinase C (PKC) activation was involved in IL-1alpha signaling.

Conclusions:

  • IL-1alpha stimulates COX-2 expression and PGE2 production in odontogenic keratocyst fibroblasts.
  • These effects are mediated through PKC-dependent activation of ERK1/2, p38, and JNK signaling pathways, as well as the NF-kappaB cascade.