Membranes and Cell Signalling Ponnambalam Flashcards
What are lipids central role?
Biological membrane component, also serve as energy stores and many intermolecular signalling events involve lipid molecules
What does phosphoinositide lipid signalling mediate?
The effects of a variety of hormones, signalling pathways, membrane protein activity (ion channels), lipid transfer protein activity, sculpting or modulating vesicle fusion and fission in membrane trafficking.
Describe phosphoinositide lipid signalling?
Signal transduction via a phosphoinositide pathway generates the second messenger inositoltriphosophate. This triggers calcium ion release or a diacyl glycerol which activates protein kinase C.
What do phosphoinositides bind?
Pleckstrin homology domain
How are phosphoinositides localised to different intracellular locations?
PI(3)P- endosomes
PI(4)P- Golgi
PI(4,5)P2 and PI(4,5,3)P3- plasma membrane.
What does phospholipase C family regulate?
Signal Transduction
How does phospholipase C work?
PH domain – binds PI lipids
C2 domain – binds membranes in the presence of calcium ions
SH2 domain – binds phosphotyrosine epitopes
SH3 domain – binds polyproline motifs
RasGEF – acts to promote GTP exchange and activation of Ras proto-oncogene
EF hands – binds calcium ions
What is protein kinase C family linked to?
Lipid metabolism.
How do protein kinase C work?
C1 domain – binds DAG lipid
C2 domain – binds membranes in the presence of calcium ions
C3 domain – binds ATP
C4 domain – binds substrate for phosphorylation by kinase d
What is the structure of phosphoinositides?
Variable head groups, 2x fatty acyl C18-20 chains, glycerol backbone, inositol sugar attached to terminal glycerol carbon
How many types of phosphatidylinositol 3-kinase are there?
4: 1A, 1B, 2 and 3.
All have regulatory subunits.
How are the Phosphatidylinositol 3-kinase different?
1A are localised to membranes and endosomes
2 are localised to Golgi and secretory pathway
3 are localised to Golgi and endosomes.
What are sphingolipids?
Second messengers.
What are sphingolipids biological effects?
Regulates cell stress, membrane trafficking, cell survival, apoptosis, phagocytosis and macrophage degradation.
What activate GPCR?
Lipid derived compounds: eg. Prostaglandins and leukotrines
What are nuclear activators?
Lipid derived compounds eg. Steroid hormones, retinoic acid PPAR family.
How many protein kinases does the human genome encode?
~518
90 tyrosine kinases
58 receptor tyrosine kinases in 20 subfamilies
32 cytoplasmic tyrosine kinases
What are the roles of tyrosine phosphorylation?
Growth factor signalling and oncogenesis, cell adhesion, spreading, migration and shape, cell cycle control and development, gene regulation.
What domains do rector tyrosine kinases have?
Extracellular, transmembrane, juxtamembrane, tyrosine kinase and c-terminal tail.
What do receptor tyrosine kinase domains do?
Extracellular for ligand binding, transmembrane membrane anchor, juxtamembrane for negative regulation, tyrosine kinase for catalysis and c-terminal tail for signal regulation.
What does RTK activation lead to?
Protein recruitment and signalling.
Promotes oligomerisation and autophosphorylation, alter gene expression, cause signalling platform assembly, can lead to Ras and MAPK activation.
What are G-proteins?
GTP-hydrolyses [On/off] binary switches.
What are G-proteins involved in?
Cyclic AMP signalling, MAP kinase signalling, PLD signalling, Redox signalling, cytoskeletal remodelling, ion channel modulation.
What is a a G-protein complex?
Recruited by GPCRs contains a 7 transmembrane GPCR, a heteromeric G-protein and a downstream signalling proteins and enzymes.
