lect 21: cell signalling Flashcards
what are the learning objectives of this lecture?
-explain the role of each of the key molecules involved in signal transduction
-identify the key extracellular/intracellular messengers and their receptors
-explain the role of G-protein coupled receptors within a signaling pathway
-describe how protein-tyrosine kinases function in a variety of signal transduction pathways
what is the graph of the overview of cell signaling?
what are the types of signaling?
what are the basic elements of cell signaling systems?
- extracellular signal molecule (or ligand)
- receptor protein
- second messenger
-small molecules or ions that relay signals received from cell surface receptors to effector proteins - intracellular signaling molecules
- effector proteins
- target-cell responses
what are important features of cell signaling systems?
- relay (i.e. pass on the signal)
- amplify
- integrate
- distribute (more than 1 effector-> complex response)
- feedback (regulate)
what is the first messenger and second messenger? and the graph on amplification?
first messenger
-binding of single extracellular ligand (e.g. hormone, other ligand) to receptor on cell outer surface
second messenger
-enables cells to mount a large-scale, coordinated response
-leads to amplification
what are the types of feedback regulation?
what is the time scale of cellular response to signals?
what is signal transduction?
-signaling pathways consist of a series of proteins
-each protein in a pathway alters the conformation of the next
protein conformation is usually altered by phosphorylation
-kinases: add phosphate groups
-phosphatases: remove them
-target proteins ultimately receive a message to alter cell activity
what does protein phosphorylation cause?
change protein behavior
-activate or inactive an enzyme
-increase or decrease protein-protein interactions
-change subcellular location of protein
-trigger protein degradation
main types of protein kinases
-serine/threonine kinases
-tyrosine kinases
what is receptor variability?
what is deactivation of a signaling cascade?
receptor desensitization
what is the regulation of cell behavior?
-each cell programmed to respond to specific combinations of extracellular signals
-each cell type displays a specific set of receptors
-various combination of signal molecules regulate cell behavior
what are the types of extracellular messengers?
what are the receptor types?
A. ion-channel coupled receptors
B. G-protein coupled receptors (GPCRs)
C. enzyme-coupled receptors
-e.g. receptor protein-tyrosine kinases (RTKs)
what is G-protein-coupled receptors (GPCRs)?
-largest superfamily of proteins (>700) (one of the most common drug target)
-7 alpha-helical transmembrane domains
-interact with G proteins
natural ligands that bind to GPRCs
-hormones (both plant and animal)
-neurotransmitters
-opium derivatives
-chemoattractants (odorants, photons)
-result in either activation or inhibition of an effector
what are G proteins?
what activates G protein subunits?
stimulation of GPCRs activate G-protein subunits
what is the termination of G-protein coupled receptor response?
what is arrestin-mediated internalization of GPCRs?
what are some types of second messengers?
what is the signal transduction by GPCRs?
G proteins
what is the graph of cyclic AMP (cAMP) signaling?
what are phosphatidylinositol-derived second messengers?
what phospholiase C-beta?
what is the graph of the inositol phospholipid pathway?
what is the summary graph of the GPCR effector pathways?
what are enzyme-coupled receptors?
intrinsic enzyme activity (receptor itself can act like an enzyme) or associated with an intracellular enzyme
-single transmembrane domain (alpha helix)
-transduce extracellular signal through dimerization (as opposed to transformation through conformational change in GPCRs)
what is the example of enzyme-coupled receptors?
receptor tyrosine kinases (RTKs)
what are the mechanisms of RTKs?
receptor dimerization
two mechanisms:
1. ligand-mediated dimerization (e.g. PDGF) (bivalent)
2. receptor-mediated dimerization (e.g. EGF) (monovalent)
-for most RTKs, dimerization brings two kinase domains in close contact for trans-autophosphorylation
what are RTKs?
-dimerization-> activates kinase domain
-receptors phosphorylate each other (on tyrosine residues)
formation of intracellular signaling complex on cytosolic tails of receptor
-some proteins form scaffolding
-others are phosphorylated/activated-> downstream effects
what do most RTKs activate?
monomeric GTPase RAS
what is the following step in activation of monomeric GTPase Ras?
what do some RTKs activate?
PI-3-kinase-Akt signaling pathway
what is the following step in the activation of the PI-3-kinase-Akt signaling pathway?
activation of Akt promotes ___________
cell survival
what is the graph of intracellular signaling pathways activated by GPCRs, RTKs or both
