Transmembrane Receptor Enzymes Flashcards
what aer the three types of transmembrane receptor enzymes
receptor tyrosine kinase
receptor serine/threonine kinase
receptor guanylyl cyclase
what are the types of receptor tyrosine kinases
insulin receptor
human epidermal growth factor receptor(HER)
platelet derived growth factor receptor(PDGF)
vascular endotheilai growth factor receptor (VEGF)
what are the different types of receptor serine/threonin kinase
transforming growth factor B (TGF-B) receptor
activin and inhibin receptor
bone morphogenic protein(BMP) receptors
what are the type of reecptor guanylyl cyclase
atrial natriuretic peptide(ANP) receptor
GC-A
GCB
GCC receptors
what is the mechanism of receptor tyrosine kinase?
from inactive monomers, they become inactive dimers and cross phsophorylate and casue the active dimer
they can also become acitve dimers straight away, adn once they ligand bind, they result in the ligand bound active dimer, that result in the sigalling
which domain allow for auto phosphorylation of the tyrosine kinase receptors
Src homology 2 domain
how many ways can phosphorylation occure
auto phosphorylation and substrate phsophrylation
what are the pathways that lead to cellular proliferation response ? from which receptor does it occure
EGFR Tyrosine kinase activation
- Mitogen activated protein Kinase Pathway
- Phospholipase Cy pathway
- Phosphatidylinositol 3 kinase athway
Describe the Receptor Tyrosine Kinsae: PLCy pathway
When the PLCY is activaed by phosphorylation,
it converts PIP2 into DG and IP3
dag which is converted into PKC
IP3 causes CA2+ to increase
describe the receptor tyrosoine kinase:PI3K pathway
PI3 kInsae result in convertions of PIP2 into PIP3
PIP3 result in attraction of peckstrin homology with the phosphatidylinositol depdendeent kindase 1
Activation of Akt (Protein Kinase B )
promote cell survival and inhibit apoptosis by phosphorylating and inactivating pro-apoptotic proteins such as Bad and caspase-9.
describe the MAPK signaling pathway
GDP to GTP at Ras
result on Raf creation
Mak
Map kinase
list the epidermal growth factor receptor inhibitor that causes inhibition of cancer
HER1 inhibitors
drug name : Geftinib, erlotinib
biologics: cetuximab, panitumumab
list the epidermal growth factor receptor inhibitor that causes inhibition of breast cancer
HER2
small molecules: Lapatinib
biologics: Trastuzumab
Platelt derived Growth Factor Receptor Inhibitor
Imatinib for cancer
Vacsular Endothelial Growth Factor(VEGF) Receptor Inhibitor for Cancer
Sunitinib, Sorafenib
biologica: Bevacizumab
Vacsular Endothelial Growth Factor(VEGF) Receptor Inhibitor for Muscle Degeneration
Oligonucleotide drug: Pegaptanib binds and blocks VEGF actions via intravitreal injections
what are some functions the Receptor Serin/Threonine kindase : Transforming Growth Factor B Receptor are related to?
Growth Arrest
Cancer
Promote Apoptosis
Fibrosis
Angiogenesis
Immunomodulation
Atherosclerosis
Inflammation
- this thus makes it diffficult to design an inhibitor without causing any side effects
receptors of Receptor Serine/ Theronin Kinase(TGFB) when the ligand binds
They will already be in a dimer and once the receptor binds, they become heterotetramer(dimer bind with dimer)
cross phosphorylation would happen adn then the MH2 AND MH1 Rsmad would be attracted
what is SMAD
It has a mad homology1 and mad homology 2
- mad holomolgy 1 bind ot DNA while mad homology 2 bings for receptor kinase interactions and causes trasncriptional activation
For bone morphology protein what are the R smads
1,5,8
for TGF-B what are the R smad
2,3
what are cosmads
they are smad4 that combine with Rsmad to move into the nucleus and regulate gene expression
inhibitory smad
6, 7
interact with Rsmad and ensure they cannot bind tot eh DNA, thus no gene trasncription process
Drug development for TGF B receptor signaling- Anti-TFG-B mAb
Fresolimumab
Drug development for TGF B receptor signaling- TBRI Kinase inhibitor
Vactosertib
Drug development for TGF B receptor signaling- Recombinant Human Bone Morphogenic Protein
rhBMP-2- for spinal deformity
rhBMP-7- for bone nonuniors
Drug development for TGF B receptor signaling- Activin Receptor Ligand Traps
Activin Receptor Type IIB-Fc Fusion Protein
Luspatercept- Anemia in B thalassemia
Drug development for TGF B receptor signaling- Activit Receptoy type IIA-Fc Fusion protien
Sotatercept- Pulmanory Arterial hypertension(PAH)
What happens when TGF-B binds to the TBRII and TBRI recpetors
smad2or 3 will be released after the cross phosphorylation of the heterotetramer
the smad2/3 binds with the COSMAD to modulate the geen expression
Receptor Guanylyl Cyclase(GC) what are they and their ligands
there are NPR-A (GCA)- Atrial NP(ANP) and Brain NP(BNP)
NPR-B CNP from endothelial and renal cells
NPR-C clearance receptor for anp, bnp, cnp
GCC- Uroguanylin and Guanylin
GCA, GCB, GCC- are mainly in the CVS, skeletal system adn GI tract
GCD AND GCG- absent in the human
GCE AND GCF- in the retinal photoreceptors
how many domains do the Natruretic peptide receptor have
ligand binding domin
kinse homology domain
hinge region
Guanylyl cyclase domain
drugs for the Natriuretic Peptide Receptors
ANP: Carperitide, for short term acute decompensated CHF
BNP: Mesiritide: for short terms acute decompensated CHF
CNP: cenderititde for natiuresis, diuresis and cardiac fibrosis
function of PCGA
Natrurietic
aterial vasodialtion
renin and aldosterone suppressing
anti apoptotic
anti hypertrohic
lusitropic
lipolytic
function of PGCB
anti fibrotic
anti inflammatory
vascular regenerating
GCC receptor agonist
linaclotid and plecanatide
for chronic idiopathic constipation and IBD predominant constipation
and GI tumorigenesis
