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Printable Handouts
Navigable Slide Index
- Introduction
- Cytokines - definition
- Cytokines and hormones
- Role of cytokines in the immune system
- Two arms to the human immune system
- Innate immune response
- Classification of cytokines
- Classification of cytokine receptors (1)
- Principles of cytokine receptor signaling (1)
- Cytokine-receptor interaction
- Cytokine-induced receptor oligomerization
- GM-CSF receptor subfamily
- IL-6 receptor subfamily
- IL-2 receptor subfamily
- What is the impact of sharing receptor subunits?
- Sharing the subunit may lead to competition
- Sharing multiple subunits explains redundancy
- Receptor subunits and modulated responses
- Cytokine-mediated intracellular signaling
- Principles of cytokine receptor signaling (2)
- Phosphorylation
- Classification of cytokine receptors (2)
- Kinases
- TGF receptors carry kinase activity (1)
- TBRI-mediated Smads activation
- TGF receptors carry kinase activity (2)
- TGF receptors carry kinase activity (3)
- Cytokine receptors directly recruit kinases
- Janus kinase family (JAK1, JAK2, JAK3, TYK2)
- JAK-STAT in interferon signaling (1)
- JAK-STAT in interferon signaling (2)
- Signal transducer and activator of transcription
- Model applies to other cytokine receptors
- Recruitment of kinases through adaptors
- Principles of cytokine receptor signaling (3)
- Protein ubiquitination (1)
- Protein ubiquitination (2)
- TLR/IL-1R superfamily
- IL-1 receptor recruits IRAKs through MyD88
- IRAK (interleukin-1R-associated kinase) family
- TAK1-dependent NF-kappa-B activation
- IRAK4 the upstream kinase is a drug target
- Generation IRAK4 kinase-inactive knock-in mice
- IRAK4 required for IL-1-induced gene expression
- Coupling NF-kappa-B with mRNA stabilization
- IRAK4 required for IRAK1 and IRAK2 modification
- Helical assembly in the MyD88-IRAK4-RAK2
- Myddosome complex
- IL-1R and IL-17R
- IL-17-IL-17R family
- Act1/CIKS
- SEFIR domain
- Act1 recruited to IL-17R through SEFIR domain
- Act1: a key component for IL-17R signaling
- Computational modeling of Act1-SEFIR domain
- Act1: ubiquitin E3 ligase
- Act1-mediated TRAF6 ubiquitination
- Act1 and TRAF2/5 model (1)
- Act1 is phosphorylated upon IL-17 stimulation
- IL-17 induces formation of Act1-IKKi complex
- S311 is located with the TRAF binding site
- Act1 and TRAF2/5 model (2)
- TRAF6 (1)
- TRAF6 (2)
- Act1-TRAF5 interaction model
- TRAF5
- TRAF2
- Act1 and TRAF2/5 model (3)
- Three types of cytokine receptors
- IL-1 versus IL-17 signaling in autoimmunity
- IL-1 effect on TH17
- EAE - a model for Th17 effector function (1)
- EAE - a model for Th17 effector function (2)
- Induction of EAE
- EAE in IL-17RC-deficient mice
- EAE in Act1-deficient mice
- Act1 is required for the effector stage of EAE
- Amelioration of EAE in CNS- Act1-deficient mice
- IL-1R is required for MOG-induced EAE
- IRAK4 kinase is required for MOG-induced EAE
- Reduced Th17 activation in IRAK4KI mice
- Specificity - time and location
- Conclusions
Topics Covered
- Cytokine receptor signal transduction
- Role of cytokines in the immune system -Classification of cytokines and cytokine receptors
- Receptors with intrinsic kinase activity (TGF-TGFR family)
- Cytokine receptors directly recruit kinases (The four-alpha-helix bundle cytokine family; JAK-STAT signaling)
- Cytokine receptors recruit kinases through adaptors (IL-1R and IL-17R)
- Specificity of cytokine signaling
- Update talk: Myddosomes in TLR-IL-1R signaling
- Update talk: IRAK2 kinase domain
- Update talk: IL-17 signaling pathways
- Update talk: Act1 as an RNA binding protein
- Update talk: IL-17A induces Act1 binding to pro-inflammatory mRNAs
Talk Citation
Li, X. (2024, March 31). Principles of cytokine-receptor interactions and signal transduction [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 21, 2024, from https://doi.org/10.69645/RCWV3681.Export Citation (RIS)
Publication History
Financial Disclosures
- Dr. Xiaoxia Li has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Update Available
The speaker addresses developments since the publication of the original talk. We recommend listening to the associated update as well as the lecture.
- Full lecture Duration: 51:55 min
- Principles of cytokine-receptor interactions and signal transduction: an update Duration: 15:39 min
Principles of cytokine-receptor interactions and signal transduction
A selection of talks on Immunology & Inflammation
Transcript
Please wait while the transcript is being prepared...
0:00
In this lecture, we'll focus on the
Principles of Cytokine-Receptor Interactions and Signal Transduction.
0:10
The word cytokines in Greek is cyto means cells,
and kinos means movement.
Cytokines are small proteins released by cells of the immune system for
intercellular communication in the generation of an immune response.
0:29
Traditional hormones are secreted by glands into
the bloodstream to act on distant cells in the so-called endocrine fashion.
Cytokines differ from classical hormones in that they are produced by
a number of tissues or cell types rather than by specialized glands.
They generally act locally in paracrine acting on
nearby cells or autocrine manner acting on cells that secrete them.
1:02
Since cytokines play fundamental roles in the immune response,
I'll first briefly introduce our immune system.
1:12
There are two arms to our human immune system.
Innate immunity is what we're born with.
It is highly conserved.
It is our first-line host defense against
an infection through pattern recognition of conserved
the molecules associated with microorganisms,
the microbial non-self by our pattern recognition receptors.
Innate immunity is linked to adaptive immunity
through the activation of professional antigen-presenting cells.
Adaptive immunity elicits specific immune responses against
the specific antigens through the activation of T and B lymphocytes.
It is critical to note that adaptive immunity also feeds
back to innate immunity through both humoral and cellular responses.
Numerous studies have now indicated that this dysregulation of
either innate or adaptive immunity can lead to
autoimmune inflammatory diseases and also contribute to tumorigenesis.