Lecture Two - intracellular signal transduction pathways Flashcards
(34 cards)
what is a signalling pathway? give the definition
binding of a ligand to a receptor initiates a signal transduction pathway
intracellular signal transduction pathways process information.
what information is given to a cell to ilicit a response? a
environmental stresses
signals from other cells
extracellular matrix
nutrient signals
internal states - homeostasis, cell cycle
what biological outputs occur due to information given to a cell?
gene expression
morphological changes
production/secretion
growth/division
senescense/death
what is core concept one in intracellular signalling?
environmental changes (internal or external) must be sensed by the cell
via the activation of cell surface receptors and intracellular nuclear receptors
what is core concept two in intracellular signalling?
cells respond to these environmental changes by activating or inhibiting the activity of specific intracellular signalling pathways to change their biological function/fate
by conformational changes in intracellular signalling molecules, changes in protein structure (post-translational modification), and generation of second messengers
what is an example of conformational changes in intracellular signalling molecules?
heterotrimeric G-protein complexes
* non-active GPCR - G⍺ subunit is bound to GDP is complexed with Gβ𝛾 subunits and is inactive
ligand-bound GPCR - G⍺ subunit releases GDP and binds GTP, this changes its conformation causing the Gβ𝛾 subunbit to dissociate, both of the free G⍺ and Gβ𝛾 subunits are now active
receptor dimerisation and activation (enzyme coupled receptors)
* binding of a signal molecule in form of a dimer activates the catalytic domain
* binding of a signal molecule activates an associated enzyme
what is the result of a change in protein structure (post-translational modification)?
can lead to changes in protein-protein interactions e.g. phosphorylation
can lead to changes in protein expression by triggering protein degradation e.g. ubiquitylation
what is eukaryotic cell division initiated by?
mitogens and growth factors that act to satisfy the restriction checkpoint (R)
PDGF binds to its cell surface receptor resulting in signal transmission, and transcriptional response, resulting in cell growth and cell division, by regulating the entry of cells into the cell cycle and progression to the restriction point.
what regulates the restriction checkpoint?
G1 phase CDK’s and cyclins
what is a cyclin?
regulatory subunit
expression levels controlled by rates of protein synthesis vs protein degradation.
G1 phase cyclin = cyclin D
what is CDK?
catalytic subunit
protein kinase activity controlled by cyclin binding and protein phosphorylation
G1 phase CDK’s = CDK4 & CDK6
where are M-phase cyclins degraded?
at the spindle assembly point (SAC) by the APC/C ubiquitin lipase to promote chromosome segregation in anaphase
what does PDGF stand for?
platelet-derived growth factor
what does CDK stand for?
cyclin-dependent kinase
what are examples of second messengers?
AC - adenylyl cyclase
PLC - phospholipase C
give the process catalysed by adenylyl cyclase.
ATP produces cAMP using adenylyl cyclase as a catalyst releasing a pyrophosphate molecule
cAMP is only produced in response to GPCR activation
what activates the β isoform of phospholipase C?
G⍺q downstream of GPCR’s
what activates the 𝛾 isoform of phospholipase C?
kinase-linked receptors
what is the equation of the reaction that phospholipase C catalyses?
PI 4,5 -bisphosphate [PI(4,5)P2]
> diacylglycerol > activates protein kinase C
> IP3 > releases Ca2+ from the endoplasmic reticulum
what does IP3 stand for?
inositol1,4,5-triphosphate
what is the process of the PKA signalling pathway?
binding of 4 cAMP molecules to an R2C2 complex induces a conformational change of the regulatory subunits to release the two catalytic subunits which are then free to phosphorylate proteins in the cytoplasm
give examples of the proteins phosphorylated by active protein kinase A
- several Ca2+ handling proteins are phosphorylated by active PKA catalytic subunits > muscle contraction/relaxation
- PKA regulates the activity of several metabolic enzymes > release of glucose from glycogen
- PKA regulates the transcription of specific genes e.g. active PKA catalytic subunits travel into the nucleus and activate CREB by phosphorylation. active CREB activated CBP at the CRE which results in gene transcription of the target gene.
what does PKA stand for?
protein kinase A
what does CREB stand for?
cAMP-response element binding protein
