Cytokine Receptors
Mohammad Mufarreh
Cytokine -mediated effects
• Cell growth.
• Cell differentiation.

• Cell death.
• Induce non-responsiveness to other
cyto...
How do cytokines tell cells what to do?
• Produced by cells as part of normal
cellular activity and/or the result of
envir...
Cytokine Receptors
• Cytokine receptors are receptors that
bind cytokines.
• Binding to specific receptors is essential
fo...
Cytokine Receptors
Cytokine Receptors
Cytokine Receptors
Cytokine Receptors
Cytokine Receptors
Cytokine Receptors
Cytokine Receptors
TGF-beta Receptors
TGF-beta Receptor 1
TGF-beta Receptor 2
3 Subfamilies of Class I Cytokine Receptors
Type I cytokines whose receptor share c chain
IL-2 receptor family (common

c

chain, CD132)

heterodimerics

IL-2

IL15

...
Interactions between Cytokine-specific Subunits
and a Common Signal-transducing Subunit of
Cytokine Receptors.
Interactions between Cytokine-specific Subunits
and a Common Signal-transducing Subunit of
Cytokine Receptors.
Competition of Ligand-binding Chains of
Different Receptors for a Common Subunit
Can Produce Antagnistic Effects between
C...
3 Forms of the IL-2 Receptor

(CD25)
3 Forms of the IL-2 Receptor

Intermediate affinity

Expression:

NK cells
Resting TC

High affinity

Low affinity
IL-2Ra,...
JAK-STAT Signal Transduction Pathways
of Cytokine Receptors
• JAK: Janus kinases. (or Just Another
Kinase).
• STAT: Signal...
JAK-STAT Signaling Pathway
JAK-STAT Signaling Pathway
JAK-STAT Signaling Pathway
JAK-STAT Signaling Pathway
The Regulation of Th Subsets by Cytokines
Transcription Factors: Th1 vs. Th2
Seven-transmembrane-domain receptors signal
by coupling with trimeric GTP-binding
proteins
Other signaling pathways
Suppressor Of Cytokine Signaling (SOCS) target
Jaks to downregulate signaling

cytokine inducible family of genes which fu...
Cytokine receptors in disease

• Hyperactivating mutations affecting type I
cytokine receptor signaling pathway are found
...
Cytokine and cytokine receptor polymorphisms in
infectious disease
• The capacity of monocytes to produce TNFα
varies more...
Cytokine and cytokine receptor polymorphisms in
infectious disease
• Mutations in the receptors for IL-12 and IFNγ,
both c...
Impaired cytokine signaling in human disease

• Constitutive activation of Jak/Stat pathway in
leukemia, HTLV1 transformed...
Cytokine Receptors, Mohammad Mufarreh Ali
Cytokine Receptors, Mohammad Mufarreh Ali
Cytokine Receptors, Mohammad Mufarreh Ali
Cytokine Receptors, Mohammad Mufarreh Ali
Cytokine Receptors, Mohammad Mufarreh Ali
Cytokine Receptors, Mohammad Mufarreh Ali
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Cytokine Receptors, Mohammad Mufarreh Ali

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A detailed description of the nature, types, and mechanisms of action of cytokine receptors.
Describes the different functions of cytokines and their role in the regulation of the immune response.
Cytokine receptor signalling and their regulation and the role of cytokines in disease is also covered briefly.

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Cytokine Receptors, Mohammad Mufarreh Ali

  1. 1. Cytokine Receptors Mohammad Mufarreh
  2. 2. Cytokine -mediated effects • Cell growth. • Cell differentiation. • Cell death. • Induce non-responsiveness to other cytokines/cells. • Induce responsiveness to other cytokines/cells. • Induce secretion of other cytokines.
  3. 3. How do cytokines tell cells what to do? • Produced by cells as part of normal cellular activity and/or the result of environmental trigger. • Cytokines are not specific to antigens. • Bind to receptors on cells. • Trigger signal transduction pathways. • Initiate synthesis of new proteins.
  4. 4. Cytokine Receptors • Cytokine receptors are receptors that bind cytokines. • Binding to specific receptors is essential for cytokines to carry out their functions. • Cytokine receptors may be both membrane-bound and soluble. • Soluble cytokine receptors are extremely common regulators of cytokine function.
  5. 5. Cytokine Receptors
  6. 6. Cytokine Receptors
  7. 7. Cytokine Receptors
  8. 8. Cytokine Receptors
  9. 9. Cytokine Receptors
  10. 10. Cytokine Receptors
  11. 11. Cytokine Receptors TGF-beta Receptors TGF-beta Receptor 1 TGF-beta Receptor 2
  12. 12. 3 Subfamilies of Class I Cytokine Receptors
  13. 13. Type I cytokines whose receptor share c chain IL-2 receptor family (common c chain, CD132) heterodimerics IL-2 IL15 IL-4 (IL-7( , c); IL-9 ( , c) IL-21 ( , c)
  14. 14. Interactions between Cytokine-specific Subunits and a Common Signal-transducing Subunit of Cytokine Receptors.
  15. 15. Interactions between Cytokine-specific Subunits and a Common Signal-transducing Subunit of Cytokine Receptors.
  16. 16. Competition of Ligand-binding Chains of Different Receptors for a Common Subunit Can Produce Antagnistic Effects between Cytokines.
  17. 17. 3 Forms of the IL-2 Receptor (CD25)
  18. 18. 3 Forms of the IL-2 Receptor Intermediate affinity Expression: NK cells Resting TC High affinity Low affinity IL-2Ra, CD25 Activated CD4+, CD8+ Tc Resting CD4+TC B cells CD8+Tc Signal Transduction: and chains
  19. 19. JAK-STAT Signal Transduction Pathways of Cytokine Receptors • JAK: Janus kinases. (or Just Another Kinase). • STAT: Signal Transducers and Activators of Transcription.
  20. 20. JAK-STAT Signaling Pathway
  21. 21. JAK-STAT Signaling Pathway
  22. 22. JAK-STAT Signaling Pathway
  23. 23. JAK-STAT Signaling Pathway
  24. 24. The Regulation of Th Subsets by Cytokines
  25. 25. Transcription Factors: Th1 vs. Th2
  26. 26. Seven-transmembrane-domain receptors signal by coupling with trimeric GTP-binding proteins
  27. 27. Other signaling pathways
  28. 28. Suppressor Of Cytokine Signaling (SOCS) target Jaks to downregulate signaling cytokine inducible family of genes which function as feedback inhibitors of signaling.
  29. 29. Cytokine receptors in disease • Hyperactivating mutations affecting type I cytokine receptor signaling pathway are found associated with several myeloproliferative diseases. • Inappropriate activation of type I cytokine receptor signaling appears to be a hallmark of a range of malignancies, including leukemias and lymphomas. • Defects in signaling by members of the IL-2 receptor family cause the majority of cases of severe combined immune deficiency (SCID).
  30. 30. Cytokine and cytokine receptor polymorphisms in infectious disease • The capacity of monocytes to produce TNFα varies more than tenfold between individuals. • Several polymorphisms within the TNFα gene have been associated with increased TNFα production and increased mortality of sepsis. • However, these associations most likely result from linkage disequilibrium with other immune response genes on chromosome 6. • Polymorphisms within the IL-1β and the IL-1RA genes (located on chromosome 2) have been linked to inflammatory disease (e.g. Rheumatoid arthritis).
  31. 31. Cytokine and cytokine receptor polymorphisms in infectious disease • Mutations in the receptors for IL-12 and IFNγ, both critical for clearance of intracellular infectious pathogens, are associated with severe recurrent infections with Salmonella species and mycobacteria. • TNFR1 mutations cause fever of unknown origin.
  32. 32. Impaired cytokine signaling in human disease • Constitutive activation of Jak/Stat pathway in leukemia, HTLV1 transformed cells. • Jak2 inhibitor as a therapeutic agent. • SCID families exhibit abnormalities in lymphocyte-specific Jak3 gene. • The same phenotype is observed in individuals with mutations in the receptor component which associates with Jak3. • Constitutively active STATs (usually stat3) in human cancers. • Defects in IFNγ signaling in lung cancer. • General role of IFNγ in tumor surveillance.

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