Receptor Tyrosine Kinase Flashcards Preview

Thanh Cell Physiology Unit III > Receptor Tyrosine Kinase > Flashcards

Flashcards in Receptor Tyrosine Kinase Deck (10)
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1
Q

mechanism of receptor tyrosine kinase activation.

A

RTK activation is driven by ligand binding –> dimerization

-can homodimerize or heterodimerize to activate signaling depending on ligand

2
Q

Epidermal growth factor receptor (EGFR) key downstream signaling event

A

Ras activation

- stimulates proliferation of cell

3
Q

Ras proteins

A

GTP binding protein.
membrane bound switches that are regulated by GAPs and GEFs

  • GDP bound: inactive
  • GTP bound: active
4
Q

molecular mechanism of stimulation of ras GTPase by RTKs

A
  1. ligand binds to RTK
  2. SH2 and Grb2 (adaptor) binds to activated receptor by PM
  3. Sos (Ras GEF) gets recruited, its proximity with membrane bound Ras…
  4. Activates Ras
    - (sos can activate even in absence of RTK stim)
5
Q

two main classes of RTK-targeted anti-cancer agents

A

EGFR as therapeutic target in cancer using 2 agents:

  1. TKI’s
  2. antibodies:
    Gefitinib
    Cetuximab
6
Q

mechanism of action of RTK-targeted anti-cancer agent:

Cetuximab

A

Anti-EGFR cetuximab blocks ligand binding site

  • -> prevent dimerization
  • -> prevents proliferation
7
Q

mechanism of action of RTK-targeted anti-cancer agent:

Gefitinib

A

Anti-EGFR gefitinib blocks ligand binding and EGFR kinase activity

  • -> blocks phosphorylation activation of receptor and intracellular messengers
  • -> stops downstream signaling
8
Q

mechanism of action of RTK-targeted anti-cancer agent:

TKIs

A
very specific (too specific)
specific to each tyrosine kinase

blocks ATP binding site –> kinase dies

9
Q

tumor cell characteristics that predict clinical response to EGFR-targeted therapeutics

A

Individuals with mutant EGFR TK is more active and more potently inhibited by gefitinib (bound with higher affinity)

10
Q

mechanism of resistance to TKI’s such as EGFR inhibitors.

A

Acquired resistance-A secondary mutation in EGFR causes individuals who initially benefited from therapy, but then acquire resistance to antibodies
=(

the 2nd mut block inhibitor binding to kinase activation site