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
Ran is a ____________ G protein
nuclear transport
Rab is a ____________ G protein
tethering vesicles
Sar1 is a ____________ G protein
vesicle formation
Rho is a ____________ G protein
actin-binding protein regulator
what does GAPs stand for?
GTPase activating proteins
what does GDIs stand for?
guanine nucleotide dissociation inhibitors
what does GEFs stand for?
guanine nucleotide exchange factors
how is the Ras-MAP pathway activated?
when a growth factor binds the extracellular domain of an RTK
what are the 4 main steps after ligand binding in Ras-MAP?
- dimerization of two receptors
- trans-autophosphorylation of cytosolic portion of the RTK protein
- SH2 domain containing protein Grb2 has high affinity for the pTyr on the RTK
- Grb2 is constitutively associated with a RasGEF called Sos
what does recruitment of Sos to the membrane do?
brings the RasGEF into close proximity with Ras, allowing GDP to be replaced with GTP = ACTIVATION OF RAS
what does Ras-GTP have a high affinity for?
protein kinase Raf
what does Raf phosphorylate?
serine and threonine residues in a protein kinase called MEK
what does MEK phosphorylate?
ERK or mitogen activated protein kinase (MAPK)
growth factor binding leads to….
cell proliferation
T or F: once Ras is in the active state, it must be inactivated to avoid continual stimulation of the Ras pathway
true
what deactivates the Ras pathway?
GTPase activating protein (RasGAP) that facilitates GTP hydrolysis
Ras mutations are common in _________
cancer
scaffolding proteins can tether different MAP kinase pathways together, ________ ____________ __________ ____________-
physically linking signalling pathways
def: activation of a common effector/2nd messenger
convergence
def: one RTK can activate 3 different pathways
divergence
steroids are ________ proteins?
soluble proteins
what are the 2 domains of a nuclear receptor?
- ligand binding domain
- DNA binding domain
what are 3 properties of the DNA binding domain of nuclear receptors?
- steroid receptors act by binding specific DNA enhancer sequences called hormone receptor elements (HRE)
- the DNA binding domain is usually two Zinc-Finger motifs
- binding to the HRE leads to either enhanced or repressed gene expression
what is the starting material for synthesis of steroid hormones?
cholesterol
def: family of hormones that promote synthesis of glucose and suppress inflammation
glucocortoids
def: regulate ion balance by promoting reabsorption of sodium, chloride, and bicarbonate ions by the kidney
mineralcorticoids
def: 8-30 amino acids in length, containing proline and positively charged amino acids (arginine and lysine)
NLS (nuclear localization signal)
def: ligands that mediate the opening of Na+ channels
neurotransmitters
