intracellular signallin Flashcards
give 4 examples of cellular responses
- change metabolic activity e.g. glucagon
- secrete and release e.g. mast cell and histamine
- changes in gene expression e.g. epidermal growth factor (EGF) activate genes
- sensory perception e.g. light activation of rhodopsin
what acts as extracellular signals? 5
- amino acids (adrenaline, dopamine, glutamate…)
- steroids
- prostaglandins (eicosanoids) - derived from arachidonic acid
- proteins and peptides
- gases (NO, CO)
4 examples of steroids
ortisol, aldosterone, testosterone, oestradoil
4 examples of proteins and peptides used in extracellular signalling
insulin
glucagon
growth factor
EGF
5 ways for cells to signal to EACH OTHER
- endocrine
- autocrine: acts on same cell
- paracrine: close by
- contact dependent (Signal is integral part of one cell and interacts directly with another cell)
- neuronal
what kind of substance do cell surface receptors bind to
- hydrophilic hormone e.g. adrenaline
- trigger response inside cell
what substances do intracellular receptors bind to
- hydrophilic hormones e.g. steroid hormones
- bind to receptor inside cell
types of signalling when signal is bound to receptor and examples
- depolarisation of membrane due to ion flow e.g. ACh
- directly activate transcription factor e.g. steroid
- generate secondary messenger e.g. glucagon - cAMP
- direct activation of enzymatic kinase cascade e.g. EGF - MAP kinase pathway
what substances are involved with signalling by membrane depolarisation
ion channels e..g ACh binding to nicotinic acetylcholine receptor
Na, K, Ca ions
describe activaton of transcription factors
- steroid hormones contain hormone binding domain, DNA domain and domain to interact with other trans factors
- binding of steroid = conformational change = DNA binding and activation of target genes
- hormone response elements in sequence of target genes
- ligand-dependent transcription factors
Give 5 examples of secondary messengers
cAMP IP3/DAG Ca2+ nitric oxide cyclic GMP
examples of secondary messengers generated by enzymes - GPCR (G protein coupled receptor)
– Activate adenylyl cyclase (adenylate cyclase)
• adenosine 3’:5’- cyclic monophosphate (cAMP)
-Activation of phospholipase C
• inositol 1,4,5-trisphosphate (IP3)
• 1,2-diacylglycerol (DAG)
what’s an example of a GPCR
B-adrenargic receptor e.g. adrenaline
what happens when a G-protein is activated
- hetrotrimeric complex
- dissociates when GTP binds.
- Free Ga subunit activate effector enzymes which produces 2nd messenger
- re-associates when GTP hydrolysed to GDP by GTPase
what does G protein dissociate into
GTP - alpha-bound subunit
By (beta-gamma) subunits
describe the structure of cAMP dependent PKA
-tetrameric enzyme
2 regulatory, 2 catalytic subunits R2C3
how does cAMP activate PKA
- cAMP binds to regulatory subunit on PKA = dissociates
- catalytic monomers are active enzymes
ATP –> cAMP –> AMP enzymes
adenylyl cyclase
phosphodiesterase
how does cAMP and PKA action affect gene expression
- PKA phosphorylates CREB (cAMP response elementat binding protein)
- CREB binds to sequences. in target genes - stimulate transcription
what does the Gq (Gaq) subunit in some GPCR do
- dissociated Gaq subunit activates phospholipase C
- cleaves inositol phospholipids in membrane (IP3, DAG)
- IP3 activates Ca channel in ER
- DAG and Ca activates protein kinase C
how does the binding of EGF activate
- autophosphorylates tyrosine residues in intracellular RTK
- proteins contain phosphotyrosine binding sites: SH2 and PTB
- adaptor roteins Grb2 and Sos bind to receptor
- activates exchange GDP-Ras–> GTP-Ras
what is Ras and describe the Ras-MAPkinase pathway
- monomeric G protein
- triggers kinase cascade
- MAPKKK activates MAPKK actives MAPK –> activates transcription factor
- no secondary messenger
what does MAPK stand for
mitogen activated protein kinase
what are the 2 types of overlap in intracellular signalling (i.e. one hormone for different receptors)
- convergence: different signals trigger diff pathways but same effect
- Cross talk: diff signals trigger diff pathways that block each other
give an example of cross talk overlap
- EGF signalling via PTK and Ras-MAPK
- adrenaline inhibits one of the steps via action of PKA
what does IP3 and DAG stand for
Inositol 1, 4, 5 trisphosphate
Diacylglycerol
what are the phosphotyrosine binding proteins in adaptor proteins in the activation of kinase cascade
SH2 (sos - homology 2)
PTB (phosphotyrosine binding)
what adaptor proteins bind to the receptor in activation of kinase cascade - EGF
Grb2 and Sos
