lipid signalling Flashcards
what determines the cellular response
the net concentration of the second messenger
what are first messengers
growth factors, hormones, ECM, receptors
what are second messengers
small molecules
what are some widely used second messengers
cAMP, Ca2+ ions and phosphoinositides.
how do phosphoinositides mediate different membrane events
act as signalling complexes in signalling pathways and act as ion channels, transporters, ion pumps in membrane protein acitvity. can also modulate vesicle fission and fusion. lipid transfer protein activity.
where are the 3 places phsphoinositides can be found
endosomes, golgi, plasmamembrane
what is the structure of PIP2
glycerol backbone, 2x fatty acyl chains attached. inositol sugar attached via phophate
what PIP2 hydrolysed by and why is it important
phospholipase C hydrolyses it to DAG and IP3
what does membrane bound PI do
recruits effectro protein to membrane where they interact with G-protiens
what is IP3
water soluble molecule. binds and opens Ca2+ channels in ER raises Ca2+ concentration in cytoplasm
what is DAG diacylglycerol
in membrane has 2 siganlling roles. when cleaved releases arachidonic acid and can activate protein kinase C by inducing translocation to plasma membrane
name a powerful second messenger and regulator og calcium flux
InsP3
what are some general observations of phospholipase C
PH domain binds PI lipids, C2 domain binds membranes when there is calcium ions, RasGEF promotes GTP exchange and activation of Ras proto-oncogene, EF binds calcium ions
name the different functions of the different C domains
C1-binds DAG lipid, C2-binds membranes in presence of calcium ions, C3 BINDS atp, C4 binds substrate for phosphorylation by kinase domain,
what is the function of class 1 PI3K
localised to plasma membrane and endosomes
function of class II PI3K
in golgi and secretory pathway
function of class III PI3K
in endosomes and golgi membrnaes
function of PI4K
in golgi and endosomes
what is phosphoinositdes bind pleckstrin homology domains (PH)
kinase C substrate in platelets.
what are eicosanoids
act near site of synthesis and catabolised rapidly. has specific physiological effects on target cells
what are prostaglandins
respond in injury or damage. control inflammation, blood flow, formation of clots and labour induction.
what are leukotrienes
respond in immune response. accompanied by production of histamine and prostaglandin. potent action on smooth muscle.
what are the effects of sphingomyelin
apoptosis, proliferation, inflammation, angionesis
what does ceramide regulate
cell stress
what does ceramide 1 phosphate activate
phospholipase A2 which stimulates production of arachidonic acid.
what is glucosylceramide implicated in
post golgi trafficking and drug resisitance in cnacer.
what does sphingosine interact with
protein kinase H regulates actin dynamics, cytoskeleton, endocytosis, cell cycle and apotosis.
what does sphingosine 1 phoospahte have effect on
endothelial cell growth, movement and inflammation.
