cell signalling Flashcards
1
Q
1st stage of cell signalling (general)
A
signal reception
- signal molecule acts as a ligand, and binds to a specific complementary site on target cell’s receptor
- ligand-receptor complex formed
- receptor protein undergoes conformational change
- and is activated
2
Q
2nd stage of cell signalling (general)
A
signal transduction
- (1) the change in conformation of receptor initiates transduction,
- triggering a (multistep) signal transduction pathway
- in which each relay protein act by altering the conformation of and this activating or inhibiting protein immediately downstream
- ∆ in conformation is usually phosphorylation => phosphorylation cascade
- (2) the change in conformation may also stimulate an increase in concentration of 2nd messengers
- which then readily spread throughout cytosol by diffusion
- and bind to relay proteins and alter their behaviour
=> thus allow cells to mount large-scale, coordinated response following stimulation by single signal molecule
3
Q
3rd stage of cell signalling (general)
A
- last activated protein in signal transduction pathway triggers a cellular response
- types
- cytoplasmic response: involves mainly changes in cell metabolism
(e.g. activation of enzymes) - nuclear response: involves changes in gene expression
(e.g. turning specific genes on or off, thus resulting in synthesis of enzymes)
- cytoplasmic response: involves mainly changes in cell metabolism
4
Q
role of protein kinase (PK) in cell signalling
A
- mode of action: transfers phosphate groups from ATP to a protein (i.e. phosphorylation)
- in signal transduction pathway, it phosphorylates and activates PK
-> thus turning on signal transduction pathway
5
Q
steps of cell signalling involving GPLR receptor protein
A
- signal reception
- signal molecule (ligand) binds to specific complementary site on GPLR
- resulting in change in conformation
- and GPLR being activated - signal transduction
- activated GPLR has an increased affinity for G protein
- thus binding to inactive G protein
- which result in G protein undergoing conformational change (GTP replace GDP bound to protein)
- and thus being activated
- G protein then dissociates from GPLR and diffuses along membrane
- (a) binds to target protein (usually enzyme)
- alters enzyme activity
- initiate signal transduction pathway
- (b) binds to adenyl cyclase
- and activates it
- activated adenyl cyclase then catalyses synthesis of many molecules of cAMP
- which binds to and activates PK A, which then phosphorylates other proteins - cellular response
- last activated molecule in STP triggers cellular response
- intrinsic GTPase activity of G protein hydrolyses its bound GTP to GDP
-> G protein inactivated
-> leaves target protein or adenyl cyclase
-> now available for reuse
6
Q
steps of cell signalling of RTK receptor protein
A
- signal reception
- signal molecule (ligand) binds to subunit of RTK
- resulting in aggregation and dimerisation of RTK
- activation of tyrosine kinase acitivity
- resulting in auto/cross phosphorylation
- thus resulting in a fully activated RTK protein - signal transduction
- each relay protein recognises and binds to a specific phosphorylates tyrosine
- undergoes conformational change and is activated
- goes on to initiate signal transduction pathway
=> characteristic of RTKs:
ability to trigger more than one different signal transduction pathway from a single ligand-binding event
-> activate several different cellular responses
-> display significant functional diversity - cellular response
- last activated molecule of each STP triggers a cellular response
7
Q
structure of GPLR protein and how it relates to function
A
- S1: hydrophilic aa residues form the inter-helical loops and N and C termini
F1: enable EXTRAcellular and INTRAcellular domains to be soluble in aq medium and also interact with water-soluble ligands and G protein - S2: hydrophobic aa residues are primarily found in the (7 transmembrane) a-helices + HI exist bet a-helices and bet a-helices and hydrophobic fatty acid tails of phospholipids in membrane bilayer
F2: enables membrane-embedded domain to be stabilised and embedded within the phospholipid bilayer - S3: extracellular domain contains specific aa at signal-binding site
F3: enables signal-binding site to have specific 3d conformation that allows for interaction with a specific ligand - S4: intracellular domain contains specific aa at G-protein interaction site
F4: enables G-protein interaction site to have specific 3d conformation to bind and activate G-protein - S5: binding of ligand to GPLR causes a conformational change in protein, allowing it to interact with G-protein
F5: enables GPLR to initiate signal transduction pathway via activation of G-protein
8
Q
advantages and significance of multistep pathways in cell signalling
A
- signal amplification
- provide more opportunities for coordination and regulation
- contribute to specificity of response
9
Q
elab on signal amplification
A
- features
- at each step of cascade, no of activated products is much greater than in preceding step
- small no of extracellular signal molecules is sufficient to elicit a cellular response
- response of target cell is large, as a large no of activated molecules is produced at the end of the signalling cascade
- possible bcos of
- presence of multiple steps in STP
- persistence of proteins in active form long enough to process numerous molecules of substrate before becoming inactive
10
Q
elab of regulation of cell signalling
A
- signal termination, whereby receptor and other components of STP are returned to their inactive states
- must occur in order for cell to continually respond to incoming signals
- mechanisms
- PP activity
- intrinsic GTPase activity of G protein
- phosphodiesterase activity
- enzyme which catalyses conversion of cAMP to AMP
11
Q
elab on specificity of cell signalling
A
- specific response is due to specific combi of
- signalling proteins (including receptor proteins),
- relay proteins in STP
- and proteins needed to carry out response
- thus, if 2 cells receive the same signal, but differ in one or more of the proteins
-> diff STP are activated
-< different cellular response
12
Q
regulation of blood glucose concentration (high blood glucose)
A
- [blood glucose] > 90mg/100ml (set point)
- change is detected by islets of Langerhans of pancreas
- B cells of islets of Langerhans are stimulated to secrete more insulin
- insulin (ligand) binds to insulin-receptors (RTK) -> signal transduction pathway, where activated downstream relay protein stimulates
- (liver, skeletal muscle and adipose cells) migration to and fusion of cytoplasmic vesicles carrying GLUT-4 glucose transporters with plasma membrane
-> increase no of glucose transporters in plasma membrane
-> increase rate of glucose uptake via facilitated diffusion into cells - (skeletal muscle and liver cells) glycogenesis (synthesis of glycogen from glucose)
-> increase rate of glucose storage - (adipose cells) lipogenesis (excess glucose is stored as triglycerides)
-> increase rate of glucose storage
- (liver, skeletal muscle and adipose cells) migration to and fusion of cytoplasmic vesicles carrying GLUT-4 glucose transporters with plasma membrane
- once set point is attained, negative feedback mechanisms prevents further release of insulin
13
Q
regulation of blood glucose concentration (low blood glucose)
A
- [blood glucose] < 90mg/100ml (set point)
- change is detected by islets of Langerhans of pancreas
- a cells of islets of Langerhans are stimulated to secrete more glucagon
- glucagon (ligand) binds to glucagon receptors (GPLR) -> production of cAMP
-> activation of PK A
-> phosphorylation cascade set off, where activated downstream relay protein stimulates- (skeletal muscle and liver cells) glycogenolysis
(breakdown of glycogen to glucose) - (adipose cells) lipolysis
(triglyceride breakdown)
=> both results in more glucose diffusing into bloodstream, thus increasing [blood glucose]
- (skeletal muscle and liver cells) glycogenolysis
- once set point is attained, negative feedback mechanisms prevents further release of glucagon
