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  • Created by: jo bill
  • Created on: 21-12-14 12:28

cytokines

  • cytokines are small secreted proteins that by binding to transmembrane receptors regulate cell-            
  • - survival, proliferation, differentiation, activation
  • cytokines play especially key roles in immune, hematopoietic and neuronal cell lineages

receptor families

  • cytokines signal throgh transmembrane receptors that can be grouped according to their extracellular and cytoplasmic domains
  1. tyrosine kinase receptors
  2. serine threonine kinase receptor
  3. class-1 cytokine receptors
  4. class2 cytokine receptors
  5. tumour necrosis factor-related
  6. immunoglobulin superfamily (non-RTK)
  7. G-protien coupled receptors
  • examples: 
  1. leptin
  2. growth hormone
  3. prolactin
  4. erythropoeitin
  5. thrombopoietin
  6. GCSF
  7. IL-3,5
  8. GMCSF

4-helix bundle cytokines

  • all class 1 and 2 cytokine receptors bind ligands that have a common four-alpha helical strucutre

receptor features

cytokine class 1 receptor

  • extracellular- WSXWS motif, 4 conserved cysteine residues
  • intracellular - NO INTRINSIC KINASE ACTIVITY, conserved membrane-proximal alpha-helical segment that binds JAKs

cytokine class 2 receptors

  • extracellular- 4 conserved cystienes
  • intracellular - as above

JAK-stat pathways

  • JAK : cytoplasmic tryosine kinase 
  • activate kinase and pseudo kinase domain
  • receptor binding domain
  1. cytokine receptors without ligand binding
  2. dimerization and phosphorylation of activation lip tyrosines
  3. phosphorylation of additional tyrosine residues
  4. into nucleus; binds DNA and activates transcription
  • short term regulation : JAK2 deactivationn by SHP1 phosphate
  • long term regulation: signal blocking and protein degradation by SOCS proteins

specifity in thein thte JAK-STAT pathway

  • hundreds of cytokines
  • >50 class 1 and 2 REceptors
  • 4 family me,bers : JAK, JAK2/3, TYK2
  • 7 family memebers : STAT1, 2, 3, 4, 5a, 5b, 6
  • the amino acid sequences of the rece[ptor cytoplasmic domains determine the H=JAK/STAT pairing

STAT : signal transducer and activator of transcription

  • transcriptional activation domain
  • protein-protein interaction domains
  • DNA binding Domain ( bind to cytokine-receptors
  • SH2 domain/dimerization domain
  • c-terminal tryosine

additional pathways

  • STATs are not the only protein that bimds phosphorylated tyrosines on…

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