Lecture 23 - Cell Signalling & Transmission III Flashcards
____ signalling pathways often regulate differentiation, cell division, and survival
RTK
def: signals/messengers that stimulate cell growth in dividing cells
growth factors
what does extracellular ligands binding result in?
dimerization of the receptors
what do the ligand-bound receptors do to the cytoplasmic domains of the receptors?
trans-auto-phosphorylate the cytoplasmic domains of the receptors
how are cytoplasmic signalling molecules activated?
by binding to phosphorylated tyrosine on the active receptor
cytoplasmic signalling molecules associated with the receptors through ______ and ______ domains
SH2 and PTB
def: ~100 amino acids long and contain a conserved binding pocket that interacts with pTyr
SH2 domains
what determines the specificity of different SH2 domains?
the amino acids surrounding the phosphorylated tyrosines
what does the extracellular domain of a pTyr do?
binds ligand
what does the single transmembrane helix of a pTyr do?
participates in dimerization
what does the dimerization/aggregation of a pTyr do?
activates the RTK(generally)
what does the large cytosolic domain of a pTyr do?
location of the kinase, phosphorylation target sites, and SH2 binding site
def: act as linkers enabling two or more proteins to form a signalling complex
adaptor/scaffolding proteins
what is a Grb2 an example of?
an adaptor protein
the SH2 domain of Grb2 binds to RTKs, while the SH3 domain is constitutively associated with _____
Sos
The PTB domain of IRS binds to ______s, leading to the phosphorylation of IRS tyrosines
RTK
the SH2 domain of STAT binds to ____, which phosphorylates tyrosine in ______. this allows STAT to dimerize, forrming a _________ _________ ___________ that translocated to the nucleus and activate gene expression
RTK, STAT, functional transcription factors
signalling enzymes, equipped with SH2 domains, can directly associate with RTKs, these can include:
- protein kinases
-protein phosphatases - lipid kinases
phospholipases
GTPase activating proteins
what are the 3 ways activation occur in protein pTyr and signal transduction?
- recruitment of the enzymes to the membrane, placing them in close proximity to their targets
- binding of the pTyr can result in conformational changes ini the catalytic domain increasing/decreasing the catalytic activity
- phosphorylation of the enzyme to increase or decrease the catalytic activity
how does termination of TRK signalling occur?
through internalization of the receptors, essentially the same pathway as GPCRs termination
T or F: RTK’s do not require Arrestin
True, they have a short motif in their cytoplasmic domain that can interact with AP2
in RTK termination, what are the 3 possible outcomes?
- receptor signalling can resume within the endosome
- the receptor can be trafficked to the lysosome for degradation
- the receptor can be returned to the cell surface
def: if a receptor returns to the cell surface, they can resume signalling
re-sensitization
Ras is a ____________ G protein
signal transduction
