Cell Signalling Flashcards
Explain the significance to the alpha and beta cells of their blood supply. [3]
They detect the change in blood glucose conc from the set point→ secrete hormones glucagon and insulin respectively directly into bloodstream→ hormones travel quickly to their target organs
Outline the main stages of cell signaling
- Ligand binds to specific and complementary (in 3D shape and charge) extracellular ligand-binding site of the receptor of a specific cell
- Signal transduction: converts extracellular signal to a specific intracellular response
- Conf Δ in intracellular domain of receptor–> activates receptor and relay proteins.
- phosphorylation cascade: phosphorylation/dephosphorylation by kinase/phosphatase → activation/inactivation of protein in the next step
- Signal amplification: one mlc acts on many other mlcs→ ↑ no. of activated relay proteins→ sufficiently large response from relatively small no. of signal mlcs - specific cellular response triggered, for example
- metabolic enzymes
- gene regulators - Termination
Explain how struc of G protein-coupled receptor (GPCR) is related to its function
- A cell sf receptor that initiates signal transduction→ cellular response
- Single polypeptide folded into globular tertiary protein
- Extracellular N-terminus, intracellular C-terminus
- *7 pass transmembrane protein w 7 ɑ-helices
- *Intracellular domain has a G-protein binding site
- *Extracellular loops has a ligand-binding site, where specific signal binds to GPCR→ conf change→ activate G protein by exchanging its bound GDP for GTP
- How it’s embedded:
- Aa w hydrophobic R groups interact w h.core of p.lipid bilayer
- Aa w hydrophilic R groups arranged inwards→ interact w aq cytoplasmic and extracellular regions/hydrophilic phosphate heads of p.lipid bilayer.
Explain the role and nature of 2nd messengers (cAMP) / Describe how cAMP increases blood glucose concentration
cAMP is the secondary messenger: small, non-protein, water-soluble mlcs, able to diffuse quickly throughout the cytosol to activate many other relay mlcs/PKA→ activate many enzymes involved in breakdown of glycogen to produce large amount of glucose, which are released into bloodstream
What are the advantages of having a signal transduction pathway?
- Facilitate signal amplification
- Multiple responses to 1 signal mlc, as it triggers multiple signal transduction pathways (e.g. insulin effects)
- Multiple checkpoints for regulation: several steps in signalling pathway can be regulated & controlled→ regulate cellular response
- Ensures specificity: specific signal binds to specific & complementary (in shape) ligand binding site of receptor→ specific pathway in each cell type→ specific response
- Signal mlc can activate many diff cells simultaneously (e.g. insulin→ liver, muscle cell etc.)
- Signal can activate genes in nucleus without the need to move into nucleus
Why can the same ligand result in different responses in different cells/cells of different stages in same tissue?
diff genes expressed→ diff relay mlcs and signalling pathway→ diff response
(termination) Explain how cellular response can be regulated at reception
- enzymes degrade signal mlc→ prevent ligand from binding
- endocytosis of ligand-receptor complex→ prevent signal transduction from continuing
(termination) Explain how cellular response can be regulated during signal transduction
- ↑ phosphatase activity to inactive relay mlcs→ inhibit signal
- Produce inhibitors that bind to ligand-receptor complex/ relay proteins to prevent transduction of signal
Why is there a need for termination/regulation of signal pathways?
- ligand continue to trigger signal transduction/ mlcs downstream of cAMP continues to be activated→ response persist even wout binding of signal to receptor / continued activation
- cell cannot respond to other newer signals; responds inappropriately/excessively to a signal that’s no longer relevant
Describe the GPCR pathway for glucagon
Ligand-receptor interaction
- Glucagon secreted by ɑ-cells of Islets of Langerhans
- Glucagon binds to specific and complementary extracellular ligand-binding site of GPCR
Signal transduction
- Conf Δ in intracellular domain of GPCR such that it binds to G-protein (activate GPCR)
- GTP displace GDP on G protein→ G protein activated, translocate along cytoplasmic side of the membrane→ binds to and activates enzyme adenylyl cyclase (Δ conf)
- adenylyl cyclase catalyses conversion of ATP to cAMP
- cAMP binds to & activates Protein Kinase A (PKA), which phosphorylates another protein, starting a sequential activation of kinases & phosphorylation cascade
Response:
- *activate enzyme for gluconeogenesis (non-sugar C substrates→ glucose)
- *activate enzyme for breakdown of lipids in adipose tissue
- *activate glycogen phosphorylase enzyme (liver cells)→ breakdown glycogen into glucose
- inactivate glycogen synthase enzyme→ inhibit glycogen production
⇒ [blood glucose] ↑ back to normal
Termination: Intrinsic GTPase activity of G protein catalyses hydrolysis of its GTP to GDP→ G protein inactivated, dissociates from enzymes and available for reuse
Describe the RTK signaling pathway for insulin
Ligand-receptor interaction
- Insulin secreted by β-cells of Islets of Langerhans (exocytosis)
- Insulin binds to specific and complementary extracellular ligand-binding site of RTK
- Dimerisation (not for insulin as RTK is alrdy a dimer)→ conf Δ in intracellular domain of RTK→ activates intrinsic tyrosine kinase
- Cross-phosphorylation of tyrosine residues on intracellular domain by intrinsic tyrosine kinase
Signal transduction
- Relay proteins bind to phosphorylated tyr / RTK’s kinase activity phosphorylates relay protein → activated (signal amplification)
Response
- *trigger translocation of vesicles with glucose transporter-4 (GLUT4) to plasma membrane→ ↑ no. of glucose transporters (GLUT4) on plasma membrane→ ↑ its permeability to glucose→ ↑ uptake of glucose
- ↓ gluconeogenesis
- *↑ glycolysis: glucose oxidised/broken down by aerobic respiration to form intermediates e.g. acetyl CoA, which is used for fatty acid synthesis. Enzyme for this is also activated
- *Activate glycogen synthase, which catalyse synthesis of glycogen from glucose (liver/muscle cells)
⇒ [blood glucose] ↓ back to normal
