Cell signalling Flashcards
Outline main stages of ligand receptor interxn
Outline signal transduction (phosphorylation cascade and signal amplification)
Signal transduction is a multi step cascaded pathway, amplifies signal by 1) Phosphorylation/dephosphorylation 2) 2nd messenger
Each step more PDT than preceding step
Phosphorylation cascade: Seq. of phosphorylation rxns relay proteins phosphorylates subsequent protein kinases
Phosphotases remove phosphate grps from proteins, inactivating protein kinases
Describe ion channel receptor
Transmembrane protein subunit
1) extracellular ligand
2) gated hydrophilic channel
- Ligand binds to receptor, conformational change, channel.opens
- Ion flows in changing conc.
- Ligand dissociates, gate closes
Outline cellular response
Cells respond by
1) regulating protein/enzyme activity
2) transcription of genes
Same signal -> can have diff response
Same receptor -> diff relay proteins
Same cell w diff receptors can receive diff signals
Efficiency of signal transduction increased by scaffold proteins (activate phosphorylation cascade)
Role + nature of 2nd messenger (eg. cAMP)
Small non protein moleq/ions
Water soluble cAMP Ca2+
Lipid soluble DAG
Short-lived
ROLE:
Relay info from complex to other proteins
Bind and alter conformation of other proteins
eg. G protein activates adenyl cyclase
Which then catalyses ATP to cAMP
cAMP then activates PKA
-> Phosphorylates other proteins (transcription of genes)
Betas -> need insulin
Outline how insulin regulates blood glucose concentration. (TKR)
When blood glucose conc. above 90mg
Beta cells of ioL of pancreas release insulin
1) 2 insulin moleq bind to complementary 2 insulin receptor CSM -> LIVER & MUSCLES
- Conformational change, dimerise
2) activated dimer transmits signal to catalytic TK tail
3) TK cross phosphorylates multiple tyrosine residues
Activates insulin receptor substrate
4) IRS triggers variety of relay proteins -> responses
Increase of
- transport of GLUT glucose tpts
- glycogenesis
- glycolysis
- FAT synthesis
Decrease of
- glycogenolysis (hydrolysis of glycogen)
- gluconeogenesis (conversion to glucose)
Decrease blood glucose conc.
Alphas -> Glucagon
Outline how glucagon regulates blood glucose concentration (GPLR)
When glucose below 90mg
Glucagon released by alpha cells in ioL ONLY LIVER
- Glucagon binds to complementary GPLR activates receptor -> a. GPLR binds to inactive G protein
- G protein REPLACES GDP w GTP (activating it)
Diffuse across CSM -> binds to adenyl cyclase - Activated adenyl cyclase catalyses formation of cAMP from ATP
- High cAMP conc. activates PKA
- PKA phosphorylates & activates proteins
Increase
1) gluconeogenesis
2) glycogenolysis
Decrease
1) glycolysis
2) glycogenesis
Describe GPLR
- 7 alpha helices spanning membrane (transmembrane)
- Specific loops from binding sites for ligand & G protein
G protein
GDP -> inactive
GTP -> active
Describe TKR
Single alpha helix consisting
1. Extracellular ligand binding site
2. intracellular catalytic tail -> tyrosine kinase + tyrosine residues (Tyr is an am acid)
TK tail -> kinase enzyme catalysing phosphate grp from ATP
Advantages of cell signalling process
- Signal amplification -> small amt of signal produce large amt of pdts
- REGULATED
allows for fine tuning, each step controlled independently - SPECIFICITY
Ligand specific to certain receptors on certain cell types - Single signal molecule -> triggers multiple cellular rxns
+ Simultaneously diff cell types
Advantages of cell signalling process
- Signal amplification -> small amt of signal produce large amt of pdts
- REGULATED
allows for fine tuning, each step controlled independently - SPECIFICITY
Ligand specific to certain receptors on certain cell types - Single signal molecule -> triggers multiple cellular rxns
+ Simultaneously diff cell types
