Intracellular Signalling Flashcards
Ways a cell responds and examples
- Change in metabolic activities
Eg glucagon breaks down glycogen - Secrete and release
Eg antigen binding to mast cell stimulates histamine release - Change in gene expression
Epidermal growth factor -> cell growth - Sensory perception
Light activation of rhodopsin
Extracellular signals and examples
1. Aa Eg adrenaline 2. Steroids Eg testosterone 3. Proteins Eg insulin 4. Gases eg CO
5 ways cells signal to each other
1. Endocrine Signal travels in blood 2. Autocrine Acts on same cell that produces it 3. Paracrine Acts on neighbouring cells 4. Contact dependent Integral part of one cell interacts directly with another 5. Neuronal Electrical signal passed through a synapse
2 types of receptor and implications
- Cell surface
Hormone is hydrophilic
Triggers response in cell - Intracellular
Hormone is hydrophobic
Crosses CM
Binds to receptor inside cell
4 things that can happen after signal binds to receptor
- Membrane depolarisation
- Activation of transcription factor
- Secondary message
- Activation of enzymatic kinase cascade
How Steroid hormone receptors activate transcription factors
Steroid hormones have hormone binding domain/DNA binding domain/transcription factor domain
Binding of steroids-> conformational change-> DNA binding & transcription activation (ligand dependent transcription factors)
3 Examples of secondary messenger formation
- GPCR activates adenylyl cyclase-> cAMP formed
2. GPCR activates Phospholipase C-> ip3/DAG formed
How G proteins work
3 subunits: alpha beta gamma
Signal binds to receptor -> G proteins associate with receptor-> gdp exchanged for GTP->
Alpha dissociates-> alpha activates effector enzymes
Reassociation when GTP hydrolysed to gdp
camp dependent protein kinase a components and formation
Made of 2 catalytic and 2 regulatory subunits
Camp binds to R subunits-> tetramer dissociates-> c subunits are active enzymes
Kinase cascade through glucagon receptor
Glucagon binds to glucagon receptor
ATP converted to camp
(Camp) activates PKA
(PKA) converts phosphorylase kinase b to a *ATP
(Phosphorylase kinase a) converts phosphorylase b to a *ATP
(Phosphorylase a) converts glycogen to glucose-1-phosphate
Camp & gene transcription
PKA phosphorylates CREB (camp response element binding protein)
CREB binds to specific sequences in target genes, stimulating transcription
How is DAG and IP3 produced, what do they do. Example
Alpha subunit that has dissociates from G protein activates Phospholipase C
Phospholipase C cleaves inositol phospholipids
IP3 / DAG produced
IP3 activates Ca2+ channel in ER-> ca2+ conc in cytoplasm increases-> DAG ANDd ca2+ activate PKC
Eg adrenaline receptor
EGF- ras cascade
EGF binds to receptor-> autophosphorylation of Y residues in cytoplasmic domain (receptor tyrosine kinase) -> adaptor proteins SIS and GRB2 have ohosohotyrosine binding sites (SH2 and PTB) -> GDP ras -> gtp ras
What’s ras
Monomeric G protein
GTP ras triggers kinase cascade
MAPKKK activates MAPKK which activates MAPK which activates transcription factor
What’s convergence
Signals trigger Different pathways , same effect