Lecture 9

Question 1

RTKs

Answer 1

• 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

Question 2

MAP KKK specificity

Answer 2

• Mating factor -> kinase A -> kinase B -> kinase C -> mating response
• Osmolarity -> kinase A -> kinase domain -> kinase D -> glycerol synthesis

Question 3

Sevenless signaling

Answer 3

• RTK = Sevenless
• Ligand = Boss
• Adaptor protein = Grb2(Drk)
• Ras-GEF = Sos

Question 4

Signal through PIPs

Answer 4

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

Question 5

Tyrosine kinase

Answer 5

• Some receptor with no kinase activity
• Associate with cytoplasmic tyrosine kinases
• Mechanism of transphosphorylation and protein binding to phosphorylated receptor

Question 6

Serine/Threonine Kinases

Answer 6

• Similar to RTKs
• Extracellular ligand binding domain
• Transmembrane domain
• Intracellular kinase domain
• Kinase domains phosphorylate serine/threonine residues

Question 7

Notch signaling

Answer 7

• 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

Question 8

No hedgehog

Answer 8

• 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

Question 9

Hedgehog present

Answer 9

• 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