enzyme-coupled receptors
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what does RTK stand for
receptor tyrosine kinase
what is a receptor tyrosine kinase an example of
an enzyme-coupled receptor
what type of enzymatic activity does a receptor tyrosine kinase have
intrinsic
where in the cell are RTKs located
membranes
what are the two domains of an RTK
cytosolic and extracellular
where does a ligand bind to an RTK
extracellular domain
describe the structure of the RTK that spans the membrane
transmembrane alpha helix
describe the cytosolic domain of an RTK
it contains protein tyrosine kinase activity
list some possible ligands for an RTK
growth factors (NGF, FGF, EGF), insulin
T or F: most RTKs are monomeric
true
how is the intrinsic kinase activity of an RTK activated
binding of a ligand = dimerization = activation of kinase activity
what happens once RTKs dimerize
trans-autophosphorylation (each monomer phosphorylates the other)
what does trans-autophosphorylation do
activates kinase domains
what happens after trans-autophosphorylation
conformational change that fully activates kinase activity, then autophosphorylation
what happens to the RTK after autophosphorylation
it generates binding sites for signaling proteins which can now become activation, and now can relay the signal downstream
what pathway do RTKs activate
Ras/MAP pathway
what is Ras
a monomeric G protein
what is Ras activated by
GEF
where is Ras within the cell
anchored to the cytoplasmic side of the PM by a covalently attached lipid
T or F: Ras interacts directly with the RTK
false! there is no direct interaction
what two proteins serve as linkers between Ras and RTK
GRB2 and Sos
describe the process of indirect activation of Ras by RTK
Ras=GDP bound (inactive). GRB2 interacts with active RTK via it’s SH2 domain and with SoS via it’s SH3 domain. This brings Sos to the PM to interact with Ras. Sos=GEF=Ras is GTP bound (active). Ras can now activate a downstream effector (its target)
what 3 proteins are involved in the MAP kinase module
Raf, MEK, Erk
describe how Ras activates the MAP kinase module
Ras activates Raf via direct contact. Raf activates Mek via phosphorylation, Mek activates Erk via phosphorylation. Erk can now phosphorylate different things