Flashcards in CellSig4 - 27 Deck (27):
Characterise small GTPases
Small monomeric 21kDa proteins with intrinsic GTPase activity that can bind to and hydrolyse GTP
What modifications do many GTPases have?
Lipid modifications to target them to specific membrane sites
What family do small GTPases belong?
What region of the small GTPase is most important?
Switch region alters the protein resulting in its activation when bound
Outline the activation/deactivation cycle of small GTPases
Active (quick GTP hydrolysis) > inactive (slow removal of GDP) > inactive (quick GTP association)
What inactivates GTPase?
GAP - GTPase activating protein
What activates GTPase?
GEF - guanine nucleotide exchange factor
What sequesters GDP proteins for GTPase?
GDI - guanine nucleotide dissociation inhibitor
What is Arf?
ADP ribosylation factor - controls general aspects of membrane trafficking
What is Rab?
Ras-like in brain - regulation of vesicle trafficking, docking and sorting
What is Ran?
Ras-like nuclear - controls nuclear import and nuclear export
What is Ras?
Ras sarcoma - master regulator of cell growth and survival
What is Rho?
Ras homology - maintains cell structure and polarity
What is imperative in regulation of Arf family proteins?
Localisation of GEF
What is key to specificity of vesicle targetting?
GEF and GDI
Outline the distribution of Ran across the nuclear membrane
Ran-GTP inside, Ran-GDP outside nucleus
How is the Ran distribution maintained?
Ran-GEF in nucleus, Ran-GAP and RanBP outside
What does RanGTP do?
Targets empty importins to the cytosol
What does RanGTP do once in the cytosol?
Dissociates from importin, hyrdolysed to RanGDP and is imported
What does MAP stand for?
Mitogen activating protein
Outline the Ras pathway
Active Ras > MAP k.k.kinase (Raf) > MAP k.kinase (Mek) > MAP kinase (Erk) > internal changes
Name 3 Rho family GTPases
RhoA, Rac1 and Cdc42
What do Rho family GTPases do?
Coorfinate actin cytoskeletal organisation
What does RhoA do?
Stabilises and consolidates actin filaments into more rigid framework known as stress fibres
What does Rac1 do?
Organises new actin filaments into fynamic ruffling structures or lamellipodia
What does Cdc42 do?
Polymerises actin filaments and forms actin spijes or filopodia