Lecture 9 Flashcards
1
Q
RTKs
A
- Intracellular tyrosine kinase domain phosphorylates different targets at tyrosine residues
- auto: RTKs can act on RTKs
- trans: on different RTK molecules
- Activated RTK acts as a scaffold protein
- SH2 has two binding sites -> ensure SH2 bind specific phosphorylated proteins
- RTK activation activates RAS-GEFs -> activate MAP KKK pathway
2
Q
MAP KKK specificity
A
- Mating factor -> kinase A -> kinase B -> kinase C -> mating response
- Osmolarity -> kinase A -> kinase domain -> kinase D -> glycerol synthesis
3
Q
Sevenless signaling
A
- RTK = Sevenless
- Ligand = Boss
- Adaptor protein = Grb2(Drk)
- Ras-GEF = Sos
4
Q
Signal through PIPs
A
RTK activates PI 3-kinase -> converts PI(4,5)P2 to PI(3,4,5)P3
- PDK1 and Akt bind PI(3,4,5)P3
- PDK and mTORC2 phosphorylate Akt
- Phosphorylate Bad to release Bcl2
5
Q
Tyrosine kinase
A
- Some receptor with no kinase activity
- Associate with cytoplasmic tyrosine kinases
- Mechanism of transphosphorylation and protein binding to phosphorylated receptor
6
Q
Serine/Threonine Kinases
A
- Similar to RTKs
- Extracellular ligand binding domain
- Transmembrane domain
- Intracellular kinase domain
- Kinase domains phosphorylate serine/threonine residues
7
Q
Notch signaling
A
- Notch protein made in ER
- Notch cleaved into two pieces in golgi -> stay and move to plasma membrane
- Extracellular part directly interacts with delta on surface of other cell
- Delta-Notch endocytosed to delta expressing cell -> remainder of notch cleaved at two more sites
- Cytosolic tail of notch moves to nucleus to promote transcription of Notch target genes
- Delta repressed in cell -> active Notch target genes doesn’t differentiate
8
Q
No hedgehog
A
- Patched active in cilium -> inhibits smoothened
- SuFu binds and inhibits Gli2 and Gli3
- GPCR active -> promote cAMP synthesis -> activate PKA -> phosphorylate Gli3 cause proteolytic processing and fragment repress expression of hedgehog
9
Q
Hedgehog present
A
- Hedgehog inactivates patched
- Smoothened active
- GPCR and PKA inactive -> Gli3 not proteolytically processed
- SuFu releases Gli2 from SuFu
- Gli2 activates hedgehog target genes
- Hedgehog involved in neural tube closure, tissue patterning, stem cell renewal