4 Flashcards
what is the RTK in the R7 signaling pathway?
RTK = Sevenless
What is the ligand in the R7 pathway?
Ligand = Bride of sevenless (BOSS)
what is the GEF in the R7 pathway?
GEF = Son of Sevenless (SOS)
what do GEFs do?
guanine nucleotide exchange factors (GEFs) facilitate the exchange of GDP for GTP on small GTPases like Ras, effectively activating them.
what is the Adapter protein in the R7 pathway?
SH2/SH3 Adapter Protein = Grb2 (Drk)
what do SH2/SH3 Adapter proteins do ?
These adapters help integrate and amplify cellular signals, coordinating responses like proliferation, differentiation, and movement.
- i.e. Grb2 – Links RTKs (e.g., EGFR) to Ras activation via SOS.
what do SH2 and SH3 domains bind to?
SH2 = bind to phospho-Tyrosine Residues
SH3 = binds to Proline -rich sequences
Pathway overview (STEP) or the Sevenless Pathway ?
- BOSS binds to Sevenless, activating its tyrosine kinase activity.
- Sevenless recruits Grb2 (Drk in Drosophila), which binds SOS.
- SOS activates Ras, which then triggers the MAPK (Mitogen-Activated Protein Kinase) cascade.
- This leads to differentiation of the R7 photoreceptor, crucial for UV light detection.
what in the SOS attracts Grb2?
SOS has proline that attracts Grb2
what turns offthe Sevenless pathway?
GAPS (GTPase activating Proteins)
- GTP –> GDP
HER2/Neu and activation
- HER2/neu does not bind a ligand, but it can homodimerize
- HER2 can also heterodimerize to ligand bound HER1, 3 or 4
HER2 in rodents is called Neu **
Epidermal Growth Factor has how many RTKs?
- EGF binds 4 RTKS:
HER 1 , 2, 3, 4
** receptors are monomeric in resting state, then dimerize (homo/hetero dimerize) when active
What type of mutation in Neu will cause Constitutive activation?
Valine (V) to Glutamic Acid (E) substitution in the transmembrane domain.
This mutation causes ligand-independent dimerization, leading to constant activation of the RTK’s activity and uncontrolled signalling.
KrasG12X Mutation prevents what?
prevents GAP Hydrolysis
MAPK Pathway Cascade?
Ras (S/T)
Raf (S/T)
MEK (S/T/Y)
ERK*MAPK (S/T)
** Active MAPK translocates to the Nucleus and activates many TFs
Which MAPK protein phosphorylate tyrosine?
MEK
Of the AA’s that are most often PO4’d, which is/are essential in out diet?
Threonine – Essential. The body cannot synthesize threonine, so it must be obtained through the diet.
How and what does HERCEPTIN target ?
HER2 Positive Breast Cancer
- Herceptin is a monoclonal antibody that targets the HER2 receptor
(blocks intercellular HER2 signalling)
