Cell Signalling Flashcards
Structural features of transmembrane protein that allows it to be embedded in cell
Region that spans hydrophobic core of phospholipid bilayer is made of amino acids with non-polar R groups that form hydrophobic interactions with non-polar hydrocarbon tails of phospholipids.
Polar or hydrophilic R groups of amino acids interact with hydrophilic phosphate heads of phospholipid bilayer and aqueous environment.
GPCR
(is a class of receptors and not a specific receptor)
GPCR is a cell surface receptor found on liver cells that will bind to specific signalling molecules and initiate the process of signal transduction that converts the information of the signal into cellular response.
GPCR consists of a single polypeptide with extracellular N-terminus and intracellular C-terminus. It is a seven pass transmembrane, globular tertiary protein made of 7 a-helices connected by three intracellular and three extracellular protein loops.
[Transmembrane protein explanation]
Intracellular domain has G protein binding site for binding of G protein
Extracellular loops have ligand-binding site at which specific signalling molecule can bind to GPCR. When ligand binds to GPCR, induces conformational change in intracellular domain. Activated GPCR allows inactive G protein to bind and exchange bound GDP for GTP, activating G protein.
Generic signalling pathway
A stimulus is detected by a receptor which releases a ligand which binds to cell surface receptors on the effector. Ligand binding induces a conformational change in intracellular domain of receptor, which initiates signal transduction. THe signal is further transduced and amplified (essay: mentions PC), resulting in appropriate cellular responses. When stimulus is eliminated, results in diminished response.
Phosphatase inactivates kinase after it has phosphorylated another kinase to prevent constitutive transduction of signal.
Glucagon signalling pathway
Decrease in blood sugar level below basal level is detected by a-cells in the islets of Langerhans of the pancreas, which secrete glucagon (1st messenger).
Glucagon, which has specific 3D conformation complementary in shape and charge to extracellular ligand-binding site of GPCR on liver cells, binds and induces conformational change in intracellular domain of GPCR.
Inactive G protein binds to GPCR where bound GDP is exchanged for GTP, activating G protein. Activated G protein translocates along plasma membrane and binds to enzyme adenyl cyclase, which activates and converts ATP to cAMP.
cAMP diffuses throughout cytosol and binds to protein kinase A, activating it. Activated PKA initiates sequential activation of relay proteins known as phosphorylation cascade, until cellular response is triggered:
Activation of glycogen phosphorylase for breakdown of glycogen to glucose, which is released into bloodstream to increase blood glucose concentration.
Gluconeogenesis, for synthesis of glucose from non-carbohydrate sources
a-cells detect increase in glucose and decrease glucagon production.
Intrinsic GTPase of G protein hydrolyses GTP to GDP, deactivating it and terminating cellular response.
cAMP
Secondary messenger in the glucagon signalling pathway
Numerous cAMPs which are small, non-protein water-soluble molecules able to diffuse quickly throughout the cytosol and activate many other relay molecules/PKAs
which activate many enzymes/kinases involved in breakdown of glycogen, producing large amounts of glucose which are released into bloodstream, increasing blood glucose concentration.
Insulin
Increase in blood sugar level detected by B-cells in islets of Langerhans in pancreas of liver, which secrete insulin.
Insulin with specific 3D conformation, complementary in shape and charge to ligand-binding site of RTK on liver cells, which exist as linked dimers.
Conformational change in the intracellular domain of the receptor activates intrinsic tyrosine kinases in each subunit which cross-phosphorylate the tyrosine residues on the other subunit.
Phosphorylated tyrosine residues serve as docking sites for relay proteins, which activate by binding to them or by phosphorylation by RTK.
Phosphorylation cascade occurs where protein kinases phosphorylate other proteins eventually transduces and amplifies signal until appropriate cell response is reached
Increase the number of glucose transporter-4 (GLUT4) on cell surface membrane, increasing permeability of plasma membrane to glucose to increase uptake of glucose from the blood by these cells, causing blood glucose concentration to drop
Increase activation of enzyme glycogen synthase, which catalysis synthesis of glycogen
Glucose taken up by cells results in increase in rate of glycolysis and thus aerobic respiration, leading to production of more intermediates and which are then used for fatty acid synthesis
B-cells detect decrease in glucose and decrease production of insulin.
Advantages of cell signalling pathway
- Facilitate signal amplification: only a small number of signal molecules are needed to trigger a large cellular response as number of activated molecules increases with each catalytic step in the pathway
- Provides multiple checkpoints for regulation: several steps in signalling pathway can be regulated and controlled
1st messenger can be degraded by enzymes
Endocytosis of cell surface receptors
Inactivate relay proteins/inhibit intracellular binding
eventually regulating the cellular response of the pathway.
- Coordinated activation of many different cells simultaneously: Multiple responses to 1 glucagon molecule 1 glucagon will result in production of several secondary messengers (cAMP), cAMP can then trigger multiple signal transduction pathways to elicit different responses
- Ensure specificity: glucagon has a specific conformation complementary to ligand-binding site. Binding of specific signalling molecule to specific receptor elicits specific cellular response via specific pathway in each cell type.
