BY2EN2 Endocrinology Week 4: JAK/STAT Signalling (Cathy Slack) Each week, you will be provided with worksheets that provide an overview of what will happen asynchronously (in your own time, at your own pace) and synchronously (live with me). Please make sure you have done any of the asynchronous work required before the synchronous session to make the most of it! When you are watching recordings, please do pause and make notes as well as clarifying things that you don't understand. The slides are all available on Blackboard. Asynchronously before the session Watch the recording entitled "JAK/STAT Signalling". Read Chapter 5: STAT nuclear localisation and Chapter 8: Receptor-kinase coupling in Lim, Mayer and Pawson. Watch the recording entitled 'Physiological Effects of JAK/STAT Signalling'. If you wanted to develop a treatment for conditions associated with high levels of growth hormone e.g. acromegaly - which part of the JAK/STAT pathway would you target? Think about it and prepare to discuss in groups in the live session. Read 'The JAK/STAT signaling pathway' Rawlings et al. (2004) Journal of Cell Science 117: 1281-1283. http://jcs.biologists.org/content/joces/117/8/1281.full.pdf
Synchronous session (Thursday 22nd October at 3pm-4pm) Attend the synchronous session via Blackboard collaborate. (and take part!).
JAK/STAT Signalling Lecture: How does GH signal to its target cells to elicit a physiological response? GH synthesis: · GH is a peptide hormone. · First synthesised as a longer pre-proteins (217 amino acids). · Signal peptide anchors pre-protein to membrane of ER. . From there it is further proteolytically cleaved to form mature GH (191 amino acids long). . Once the mature peptide is formed, it is packaged away into secretory vesicles, where it undergoes exocytosis. Structure of GH: · Mature GH consists of a single polypeptide chain that folds into a four-alpha helix bundle. . Glycine-120 sits at the top of the second helix, this is essential for GH function. GH Receptor: Extracellular Domain: - 4 conserved cysteine residues - WSXWS motif Intracellular Domain: - Region that binds JAK proteins - NO INTRINSIC KINASE ACTIVITY · GHR belongs to the Cytokine Class 1 Receptor family. Other Class I Cytokine Receptors: · Homomeric receptors (identical subunits)- receptors for: o GH o Leptin o Erythropoietin o Thrombopoietin · Multimeric receptors (different subunits)- receptors for: several ILs and cytokines.