Cell signalling - G protein-coupled and Enzyme-Linked Receptor Signalling Flashcards
what are all physiological signals mediated through?
proteins
what are proteins that are receiving signals termed as?
receptors
what is signal transduction?
signals are converted to a cellular response
cell signalling is?
specific and sensitive
what does it mean when we say cell signalling is sensitive?
receptors detect conc of 10 -6 - 10 -9 molar
what do we mean when we say cell signalling is specific?
precise binding between the signal molecule and the receptor - lock and key theory
what states can receptors be in?
either an active state or an inactive state dependent on their conformation (shape)
what are ligand-gated ion channels involved in?
in homeostasis, fast synaptic events, muscle contraction
what happens when the ligand binds to the receptor?
conformational change allows transit of ions across the membrane
how fast does the ion channel open for ligand-gated ion channels?
opens in milliseconds
which processes are not involved in ligand-gated ions channels?
no intermediate biochemical processes are involved
ionotropic receptors?
ligand-gated ion channels
metabotropic?
protein-coupled receptors
GPCR receptor structure?
7 membrane-spanning alpha helices
What are GPCRs associated with?
signalling for wide range of processes: coding for more than 800 GPCRs identified
e.g. olfactionm regulation of immune responses and inflammation, homeostasis, autonomic nervous system neurotransmission, growth & metastasis of tumours
G protein - how many parts and what are they called?
3 parts - alpha, beta and gamma
GTP causes?
G protein to split in two –> alpha GTP part and the beta gamma part
what causes the biological effect?
the GTP/alpha part of the G protein binding to the enzyme/ion channel
slide 12
slide 13
how many main classes of G-protein are there and what are they?
4 main classes - they are
Gαs, Gαi, Gαq, Gα12/13
What do Gαs and Gαi do?
they produce stimulation and inhibition of adenylyl cyclase which produces cyclic AMP.
What is cyclic AMP?
cAMP is a secondary messenger that activates enzymes involved in many processes including energy metabolism, cell division and differentiation, ion transport, ion channels and contractile proteins in smooth muscle
slide 16
What are enzyme-linked receptors activated by?
a wide variety of mediators: growth factors, cytokines and hormones
what do enzyme-linked receptors have a major role in?
major role in growth & cell division, inflammation, immune responses
What are the main types of enzyme-linked receptors?
receptor tyrosine kinases (RTKs), receptor serine/threonine kinases and cytokine receptors
what is the time course of effect for enzyme-linked receptors?
mintues-hours
slide 23
What is the first stage of kinase-linked receptor activation and inactivation?
ligand binds to receptors and this leads to dimerization
What is the second stage of kinase-linked receptor activation and inactivation?
The association between the 2 intracellular domains creates an active kinase enzyme
dimerization?
two ‘walls’ of channel come together
What is the third stage of kinase-linked receptor activation and inactivation?
Tyrosine residues are phosphorylated
What is the fourth stage of kinase-linked receptor activation and inactivation?
The phosphorylated tyrosine residues act as docking sites for other intracellular relay proteins (often enzymes) which are then themselves activated
What is the fifth stage of kinase-linked receptor activation and inactivation?
A cascade of events ultimately leads to biological effect
What is the sixth stage of kinase-linked receptor activation and inactivation?
The activity of the receptor is terminated by protein tyrosine phosphatases
apoquel?
comes along and binds to binding site on receptros - causes dimerisation ofmtwo receptors molecules which axtivates the kinase enzyme - add phosphates groups itself- atrracts other enzymes currently inactive inside cell - take phosphate group and goes off to activate another enzyme and another and another etc - creates biological effect
Process continues as long as drug is attached - when it comes off the whole system is shut down
heroin?
dimorphine
