BY2EN2 Endocrinology Week 5: RTKs (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 H Complete the MCQ Blackboard quiz on insulin action - you only have one attempt! We will go through the answers in the live session. Watch the recording entitled 'Receptor Tyrosine Kinases'. Watch the recording entitled 'RTKs: intracellular signal transduction'? Read Chapter 3: Signalling enzymes and their allosteric regulation and Chapter 5: Subcellular localisation of signalling molecules in Lim, Mayer and Pawson. Read: Insulin Receptor Signaling in Normal and Insulin-Resistant States. Boucher et al. (2014). Cold Spring Harb Perspect Biol 6:a009191 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941218/pdf/cshperspect-RTK- a009191.pdf Synchronous session (Thursday 29th October at 3pm-4pm) Attend the synchronous session via Blackboard collaborate. (and take part!).
Receptor Tyrosine Kinases lecture: Structure of insulin: · Composed of two chains: A and B. · Linked together by two disulphide bonds. · An additional disulphide bond within the A chain. · Several regions are highly conserved across species: o Positions of disulphide bonds. o N and C terminal regions of A chain o C terminal region of B chain. · 3D structure is very similar across species o Before recombinant human insulin, diabetic patients were treated with pig insulin, as it is similar to human insulin, so it can bind to its receptor. H.N Phe Val Leu Ala Asn Ty Glu Gin Val Lou His Chain B Leu Va 30 amino acids Leu Gly Cys His Glu Ser Cys Arg S S Gly S Gly Gly CoOH Asn S Cys Phe Tyr lle Cys Val Gin Cys Phe Asn Gh Thr S Tyr Glu Chain A 21 amino acids Gln Ser Leu Thr Ile Cys Pro Tyr Leu Ser Lys Thr TOOK Receptor Tyrosine Kinases (RTKs): cysteine- rich domain tyrosine kinase domain EGF receptor SS SS immunoglobulin- like domain 320000 22 5 fibronectin-type-III- like domain Receptor for insulin is a member of the RTKs. Different members of the family shown on the left, they have many regions where they look similar and different. SS kinase insert region plasma membrane These RTKs are also receptors for several growth factors shown in the label. CYTOSOL insulin receptor, IGF1 receptor NGF receptor FGF receptor PDGF receptor, MCSF receptor VEGF receptor Eph receptor Most members exist as a single receptor molecule, apart from the insulin and IGF1 receptor, which is a dimer.
Typical RTK Structure: NH2 COOH Insulin Receptor: Extracellular Domain: - characteristic motifs for each subfamily - ligand binding Different motifs for different receptors. Transmembrane Domain Intracellular Domain: - most conserved between (similar between all receptors). receptors - catalytic domain - kinase