lecture 24 redone Flashcards
PH domain
proteins with PH domain bind to
phosphorylated inositol phospholipis in the plasma membrane (localises signallng)
PTB domain
binds phosphotyrosine (P-Y) residues
SH2 domain
2 domain binds phosphotyrosine residues surrounded by unique proetin sequences
SH3 binds to specfically to proline rich regions
insulin receptor is a tetrameric tyrosine kinase receptor
2alpha , 2 beta , alpha at top so binds
the IR is expressed as two isoforns
isoforn A and B
beta subunit has tyrosin kinase redisues meaning it can
phosphorylate tyrosine when activated
Shc - SH2 containing apapter protein
Shc has PTB and SH2 domain
shc can bind to insulin receptor, when they bind tyrosine is phosphorylates uncoveing a binding site for binding SH3 domain
e.g Grb2 from SH3 domain binds to Shc
IRS = insulin receptor substrate (adapter protein)
IRS1,2,3,4 contains a
PH and PTB domain
PH and PTB domain enable binding to phosphorylates insulin receptor, after binding the IRS becomes phosphorylated on tyrosines by
IR tyrosine kinase activtity
IRS has wq potential tyrosine phosphorylation sites
making it a dokcing protein for proteins with SH2 domains
PI3 kinase, Grb2 and SHP2
can bind to IRS as the have SH2 domains
insulin receptor is bound to by IRS which is bound to by Shc via the Grb2, interacts with
SOS when bound
SOS acts as a GDP/GTP exchange factor
ras ia inactive when bound to GDP ras is activtated when its exchanged for GTP. Ras GTP activates
raf
raf activtes
MAPKK
MAPKK activates
MAP- kinase whcih drives growth, differentition adn proliferation
PI3 can bind to IRS via SH2 domain, this leads to generation of
PIP3
PIP3 is a binding parter for proteins with PH domains eg
AKT
PI3K adds a phosphorylates PIP3
PDK1 binds to PIP3 and it enables the phosphorylation of a redisue on AKT
mTORC2 phosphorylates AKT
dual phosphorylation activates AKT
when AKT is phosphorylated it can phosphorylate other proteins
AS160 blocks movement of vesicles containing GLUT4 by
regulating Rab
for Ran to facilitate the movement to the membrane it needs to be bound to
GTP when AS160 prevents them binding
phosphorylation of AKT leads to phosphorylation of
AS160 leading to its inactivation causing GLUT4 to translocate
AKT phosphorylates TSC2 which regulates
mTORC1