Signal Transduction Flashcards
TRUE or FALSE: Signaling pathways consist of a series of proteins. Each protein in a pathway alters the conformation of the
next protein, usually via phosphorylation
TRUE
signal transduction is initiated by binding of a ligand (which can be ???) to its receptor (cell surface or intracellular)
(soluble or membrane-bound)
autocrine signal transduction = ???
self phosphorylated
??? = signal molecule fits binding site on complementary receptor perfectly
specificity
Key features of signal transduction:
1. specificity
2. ???
3. desensitisation/adaptation
amplification
desensitisation occurs when a receptor is shut down or ???
removed from cell surface
TRUE or FALSE: Cell signalling cannot vary in response to the same
extracellular messenger
FALSE, it can vary
acetylcholine is an example of how cell signalling varies in response to same messenger due to its effect in:
- cardiac muscle = ???
- skeletal muscle = decreased contractile rate and force
- salivary glands = secretion
increased contractile rate and force
Signalling pathways often involve protein kinases and ???
phosphatases
GPCRs: signal transducer that when bound to an external ligand, causes ??? to an effector enzyme to cause an effect which generates secondary messenger cascade
intracellular G-protein binding
Receptor Tyrosine Kinase: signal transducer that autophosphorylates when ligand binds to it, causing ???
kinase cascade
receptor guanylyl cyclase: when a ligand binds, it activates formation of ???
second messenger cAMP
adhesion receptor (integrin) binds molecules in ???, changes conformation, and thus alters its interaction with the cytoskeleton
extracellular matrix
nuclear receptor: ??? binding allows receptor to regulate expression of specific genes
steroid
gated ion channel opens or closes in response to ???
concentration of signal ligand or membrane potential
GPCRs bind to g proteins and are activated by Extracellular messengers including ???, ??? chemokines, nucleotides, light, ordants (smell) and tastants (taste)
hormones, neurotransmitters
GDP is bound to the ??? subunit and is displaced by GTP = ON switch. Hydrolysis of the bound
GTP to GDP = OFF switch
α subunit
which subunit of the GPCR dissociates upon activation of GPCR and goes off to activate the effector enzyme which goes on to activate intracellular secondary messengers like cyclic AMP
beta subunit
Receptor protein Tyrosine Kinases phosphorylate ??? and there are two types
specific tyrosine residues on proteins which signals secondary messengers
receptor protein kinases are activated directly by ??? and membrane-bound ligands such as ephrins
Extracellular ligands such as growth factors (eg: EGF) and metabolic regulators (eg: insulin)
Signal transduction using RTKs usually is terminated by ???
receptor internalisation
Activation of receptor tyrosine kinases requires receptor dimerisation which is either ligand or receptor-mediated. Dimerisation causes ???
trans-autophosphorylation
Sites of trans-autophosphorylation on RTKs provide binding sites for various cellular signalling proteins which contain two types of domains that recognise phosphorylated tyrosine residues:
* Src-homology 2 (SH2) domains
* ??? domains
phosphotyrosine-binding (PTB)
Step 1 of RTK signal transduction cascade: ??? binds to RTK and trans-autophosphorylation occurs
Growth Factor
Step 2 of RTK signal transduction cascade: Ras is activated with the GDP bound to Ras turning to GTP. This goes on to phosphorylate ??? and MAPK cascade occurs
Raf
Step 3 of RTK signal transduction cascade: after MAPK cascade, ??? factors are activated
Transcription
Step 4 of RTK signal transduction cascade: receptors are ??? This terminates the response
internalised and (in most cases) degraded by lysosomes
Second messengers are small, ??? soluble intracellular molecules
that stimulate a variety of cellular activities and are very fast
lipid and water
What is the amplification step and spreading of signal in signal transduction?
the secondary messengers such as calcium and cAMP
??? is produced by adenyl cyclase in response to a wide array of first
messengers and exerts the majority of its effects by activating protein kinase A (PKA)
cAMP
phosphotases ACTIVATE or INACTIVATE cAMP?
inactivate
calcium can increase cytosolic
calcium 10-100x in response to a variety of first messengers, release
from intracellular stores (ER) or ???
calcium influx from the extracellular environment
TRUE or FALSE calcium acts alongside calmodulin. This complex can bind various targets (eg: plasma membrane calcium pump, CaM-kinases) causing effector functions
TRUE
Calcium levels are low in the cytosol because it is ??? and the membrane is highly impermeable to the ion. Calcium channels can be transiently opened by action potential or calcium itself.
pumped out into the extracellular space
