B1.2 Flashcards
1
Q
Name the 2 types of desensitization
A
- Homologous (agonist specific)
Desensitization involves P of activated receptor by GRK. Receptor binds arrestin -> cant associate w/ Gprotein = endocytosis (receptor removed from membrane)
= LOSS Gprotein coupling - Heterologous
Desensitization by P of PKA receptor by activating kinases of PKC.
= REDUCED Gp coupling
2
Q
name diseases involving G proteins/ GPCR
A
- Loss of Function Mutations
block signaling in response to agonist(s) - Gain of function mutations
lead to constitutive, agonist-independent activation of signaling (can = cancer) - Polymorphisms
mutation in regulatory regions of gene or promoters - can cause high or low expression
3
Q
What are the 2 categories of kinase-linked receptors
A
- Receptors? with own intrinsic activity w/in receptor structure
- bind ligand & recruit kinase to receptor
4
Q
what do receptor kinases contain
A
tyrosine (Y) kinase activity
which transfer the terminal P of ATP into various important biological proteins
5
Q
what are the primary signal proteins for promoting the development of cancers.
A
constitutively active tyrosine kinases
6
Q
Name 3 types of kinase linked receptors & give examples
A
- receptor tyrosine kinases (RTKs) e.g. growth factors, TLR, Insulin receptors
- Serine/threonine kinases
e. g. transforming growth factors (TGF) receptor - Cytokine receptors
e. g. cytokines
7
Q
How may Constitutive activation of RTKs may occur
A
Activation by mutation
- mutation at the receptors making them constitutively active
Autocrine-Paracrine loops
- overexpression of the receptors or the ligands
8
Q
Name Tyrosine kinases as targets for anticancer agents
A
- Small molecule inhibitor (e.g. Iressa, Tarceva)
- Monoclonal antibody (e.g. Herceptin/Transtuzumab)
- Hsp 90 and other novel strategies (e.g. Geldanamycin)
- Antibody drug conjugate
- RNAi strategies and peptide drugs
- Inhibitors of Angiogenesis
