Membrane trafficking and vesicular transport (Receptors and their signal transduction 3) Flashcards
Receptors with tyrosine kinase activity are mostly _____ ?
growth factors
What is Ras?
a monomeric GTP-binding protein
it is also a main regulator of growth promoting pathway
What are the steps of the Growth Promoting Pathway?
- Ligand binding
• receptor changes configuration → dimerization
- Autophosphorylation → cross phosphorylate
- SH2 domain recognize phosphotyrosine residue
- Grb2 protein recruited
• adapter protein → links 2 proteins
- Ras GEF protein (SOS) activates Ras
• Ras-GDP → Ras GTP
Cascade begins until eventually MAP kinase is activated and goes to the nucleus
What is the MAP-kinase cascade?
Ras activated MAP-kinase-kinase-kinase
MAP-kinase-kinase-kinase
↓
MAP-kinase-kinase
↓
MAP-kinase
What are two intracellular noteworthy proteins (containing a SH2) that bind to an activated receptor?
PI-3 kinase
→ inhibition of apoptosis
phospholipase C gamma
→ can be activated by tyrosine kinase receptor
SH2 domain can be _____ ?
the phosphotyrosine itself
or
surrounding of phosphotyrosine
What is the function of PI 3 -kinase?
creates docking sites
PI 3 kinase phosphorylates position 3 of PI 4,5 biphosphate
producing PI 3,4,5-triphosphate
this is important because it acts as the initiating point of signaling pathways → pleckstrin homology domain
What is PI 3,4,5-triphosphate recognized by?
proteins that have the domain Pleckstic Homology (PH domain)
How is PI 3-kinase activated?
an extracellular survival signal activates a receptor tyrosine kinase which recruits and activates PI 3-kinase
What is a second pathway that can be taken by PI 3,4,5 triphosphate? What is the consequence of this?
PI 3,4,5 triphosphate
(activates)
↓
PDK1 or PKB (protein kinase B)
↓
death inhibitory protein
↓
apoptosis inhibited
consequence: increase cells without control aka cancer
What are these cells called which are uncrontollably increasing? Examples?
oncogenes
- growth factor receptors
- Ras
- PI 3-kinase
- GrB2
What are guanylyl cyclase receptors?
convert GTP → cGMP
Atrial Natviuretic Peptide (AND)
How do primary messengers stimulate guanylyl cyclase?
cGMP
↓
protein kinase
↓
target proteins
OR
for soluble guanylyl cyclase
- regulated by: Ca 2+
- binds and activates NO
- metabolized by cGMP phosphodiesterase → 5’ amp
What are serine-threonine kinase receptors?
- receptor of TGF-B
- phosphorylates and regulates SMAD-P
What are some enzyme activity-linked receptors?
- growth hormone receptor
- prolactin
- cytokines
