lec 13- cell signalling and signal transduction part 2 Flashcards
what does phosphorylation do to a protein?
changes its charge and generally leads to a conformational change which can alter ligand binding or cause an increase or decrease in activity
does GTP turn into GDP?
yes
does GDP turn into GTP?
no, it is exchanged
what does GAPS, RGS, GDI, and GEF stand for?
GAPs = GTPase-activating protein
RGS = regulators of G protein signalling
GDI = guanine nucleotide dissociation inhibitors
GEF = Guanine nucleotide exchange factors
what are enzyme coupled receptors?
they are transmembrane proteins that bind ligands, cytosolic domain either contains an intrinsic kinase activity or associates directly with kinase
what is a non-receptor kinase?
A kinase that associates with a receptor or is involved in a signal transduction pathway downstream
what is the most common type of enzyme coupled receptors?
receptor tyrosine kinase (RTKs)
what is the most common type of non-receptor kinase?
non-receptor tyrosine kinase
how many RTKs and non-receptor RTKs ae encoded by humans?
60 and 32
is tyrosine kinase the ligand for RTKs?
no, the RTKs have tyrosine kinase activity instead of tyrosine kinase binded as a ligand
what are the 4 steps of receptor dimerization?
- inactive RTKs are binded to signalling protein
- binding of signalling protein causes trans-autophosphorylation resulting in activation of kinase domains
- the trans-autophosphorylation also generates binding sites for signalling proteins
- then the activated signalling proteins relay signal downstream
what does a monomeric ligand interact with?
two receptor monomers
what promotes dimerization?
two monomeric ligands binding independently to two receptor monomers
what is trans-autophosphorylation?
when the tyrosine kinase from one monomer phosphorylates the tyrosine residues on the other creating identical monomers
what can phosphorylated tyrosine act as?
docking sites for other proteins
what do phosphorylated tyrosines bind to?
effector proteins
what do effector proteins consist of?
-Src homology 2 (SH2) domain
-phosphotyrosine-binding (PTB) domain
what is a SH2 domain composed of?
roughly 100 amino acids and contain a conserved binding-pocket that accommodates a phosphorylated tyrosine residue
what does the PTB domain bind to and what is it a part of?
bind to phosphorylated tyrosine residues and are usually present as a part of Asn-Pro-X-Tyr motif
what must each molecule recognize to bind?
the phosphorylated tyrosine in the context of other specific amino acids
what are the 4 things that SH2 and PTB domain proteins do?
- act as adaptor proteins that bind other proteins
- docking proteins that supply receptors with other tyrosine phosphorylation sites
- signalling enzymes (kinases) that lead to changes in the cell
- transcription factors
what terminates the signal transduction by RTKs?
the internalization of the receptor primarily through clatherin-mediated endocytosis
what is the fate of the internalized RTKs?
either degrade in lysosomes or return to the plasma membrane
what are other things that can happen to RTKs during termination?
- the binding of RTks to clatherin adaptor protein AP-2
-may be targeted by ubiquitin ligases to undergo ubquitination through SH2 domains or adaptor proteins
