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Announcements

Announcements. Begin literature search! Locate a minimum of 1 review article & 2 peer reviewed research articles. Type out a reference list & have a copy of the papers turned in by Feb 4 ! Worth a 10 pt quiz grade. Class I cytokine receptors:. A model for cytokine receptor interactions.

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Announcements

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  1. Announcements • Begin literature search! • Locate a minimum of 1 review article & 2 peer reviewed research articles. • Type out a reference list & have a copy of the papers turned in by Feb 4! • Worth a 10 pt quiz grade.

  2. Class I cytokine receptors: A model for cytokine receptor interactions.

  3. Composed of 2 or 3 polypeptide chains (subunits) @ least 1 cytokine binding subunit @least 1 signal transducing subunit Conserved AA seq motifs: 4 cysteine residues WSXWS On one or both subunits

  4. Fig. 12-7: Unique subunit responsible for cell signaling

  5. responsible for cell signaling

  6. responsible for cell signaling

  7. What is the impact of sharing receptor subunits.

  8. Fig. 12-8, p. 310 Sharing the signal-transduction subunit may lead to competition & antagonism:

  9. All share the same beta ST subunit! Sharing of multiple subunits can explain redundancy:

  10. Cells expressing different receptor subunits may lead to low or high affinity receptors that modulate responses.

  11. IL2 Receptor: b chain g chain a chain- only expressed on activated T cells. Required for signal transduction

  12. Multisubunit receptors allows for possible differences in how different cell types respond to a cytokine.

  13. Cytokine Binding mediates Cell Signaling Transduction

  14. Neurotransmitters Chemokine receptors - Class I receptors - Class II receptors Overview of Cell Signal Transduction Has enzymatic activity or interacts with a protein that has the enzymatic activity

  15. Signal Transductions often involves phosphorylation: • Kinase- enzyme that places phosphate groups on proteins. • Tyrosine kinase-* • Serine-threonine kinase- • Histidine kinase • Either receptor is a kinase OR associates with one. • Phosphatase- enzyme that removes phosphates • Regulatory- OFF

  16. Tyrosine kinase associated receptors

  17. Janus Kinase Family (JAKs): “2 heads”- 2 symmetrical kinase domains. Cytoplasmic tyrosine kinases Associate with cytoplasmic tails of the receptors. Function- Cytokine signal transduction depends upon a cytoplasmic protein tyrosine kinase:

  18. STATs- Signal Transducer & Activator of Txn: Contain SH2 domains: Binds phosphorylated tyr. Permits dimer formation. Activated dimers function as txn activators (DNA binding domain). Who are the activated Transcription Factors?

  19. SH2 domains creates a hole so that the tyr-P from other proteins can plug in! SH2 domain

  20. Fig 6-25, p. 165, Parham.

  21. http://binfo.ym.edu.tw/mb/images/stat_dimer.gif Model applies to other cytokine receptors: (IL2)

  22. 1. Use of individual receptors or different subfamily of receptors. 2. There are different STAT proteins & different JAKs. Recognize different genes! 3. Same STATs may recognize different genes in different cell types. How do cytokines mediate specific results in different cell types?

  23. KELSO, ANNECytokines: Principles and prospects.Immunology and Cell Biology 76 (4), 300-317.

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