Flashcards in Enzyme-Coupled Receptors Deck (6)
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12.Describe fundamental functional domains of enzyme-coupled receptors and name at least two examples of receptor tyrosine kinases.
● Extracellular signal molecule binding domain
● Single transmembrane domain
● Cytosolic domain
● Examples: Insulin receptor, ephrin receptor, nerve growth factor
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13.Describe how signaling complexes develop and the types of interaction domains facilitating these complexes.
● signal molecule binds to RTKs that causes conformational change and activates kinase.
● Auto-phosphorylation
● Phosphoryl groups serves as docking sites for intracellular signalling proteins
○ Signaling protein activation can occur by docking or through phosphorylation
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14.Describe how monomeric G proteins differ from GPCR-G proteins and the types of signaling cascades they regulate. Be able to sketch a typical kinase/phosphorylation cascade.
● RTK receives a signal, autophosphorylates and can then recruit an adaptor protein which recruits another enzyme, a GEF, a Ras activating protein, which then activates RAS (by exchanging a gdp for gtp) .
○ RAS contains a lipid anchor and is associated with membrane
○ Resembles alpha subunit of trimeric G proteins
○ Serves as a hub for signal-protein complexes
● Ras activates a MAP kinase kinase kinase (Raf)
○ Which activates MAP kinase kinase (Mek)
○ Which activates MAP kinase (Erk)
○ Which can phosphorylate target proteins and modulate enzymatic activity or gene expression
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15.Describe the activity of PI3-kinase and type of 2nd messenger produced by this enzyme.
● Lipid anchored docking sites
● PI3 kinases dock and become active when attached to Tyrosine Kinase.
● PIP2 phosphorylated to PIP3
●PIP3 is most important binding site for signaling.
○ Not cleaved by Phospholipase C
○ active till de-phosphorylated
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16.Understand how enzyme-coupled receptors contribute to programmed cell death and how inhibitors of transduction pathways can induced apoptosis.
● Activated Receptor Tyrosine Kinase → activated PI 3-Kinase → production of PIP3 → docking sites for PDK1 and AKT (PDK is a kinase that phosphorylates AKT) and together with mTOR causes activation of AKT → allows it to release from the membrane
○ Released AKT phosphorylates Bad causes release of inhibitory protein and Bad can interact with other protein
○ It’s the release of the apoptosis inhibitory protein that leads to the inhibition of apoptosis
○ Promotes cell signaling
● Without active Akt cells will die
○ Tor is target of Rapamycin; inhibited Tor downregulates Akt
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