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36 Cards in this Set
- Front
- Back
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RTK (Receptor Tyrosine Kinase) is a class type of what kind of receptors?
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Enzyme linked cell surface receptors.
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What are the two primary actions of RTK's on cells?
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1. Cell survival
2. Cell proliferation |
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Where is the kinase catalytic site within the RTK structure?
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On the cytosolic domain
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How are RTK's activated?
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A dimeric ligand binds to the receptor
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Once activated, what is the first step in RTK signal cascade?
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Autophosphorylation
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Phosphorylation of tyrosines WITHIN the kinase domain does what?
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Increase the kinase activity of the enzyme
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Phosphorylation of tyrosines OUTSIDE the kinase domain does what?
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Creates high affinity binding sites for intracellular proteins.
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Activation of Grb-2 lead to what?
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Activation of Ras
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Phosphorylated tyrosines serve as docking sites for proteins containing what kind of domains?
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SH2 domains.
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What is an important domain found within SH2 domain?
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SH3 domain
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What is the significance of SH3?
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Interacts with SOS, which regulates Ras activity.
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What does SOS do?
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Regulate Ras activity
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What is Grb2 composed of?
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Only SH3 (x2) and SH2 (x1)
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Describe the active and inactive structure of Ras.
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Active - associated with GTP
Inactive - associated with GDP |
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Give an example of a monomeric GTPase.
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Ras
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How is Ras activated?
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1. GEF (Guanine Exchange Factor) facillitates dissociation of GDP from Ras.
2. GTP will allow GTP to bind |
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What facillitates GDP to dissociate from Ras?
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GEF:SOS (Guanine Exchange Factor)
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What facillitates GTP (on Ras) to hydrolyze?
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GAP (GTPase Activating Protein)
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How is Ras inactivated?
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1. GAP binds
2. GTP is hydrolyzed into GDP |
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What is the adaptor protein that couples RTK to Ras?
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Grb2
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Activated Ras induces a kinase cascade that leads to cell what?
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Cell proliferation
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Ras induced serine/threonine phosphorylation cascade activates what protein?
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MAP kinase
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Describe the steps of how active Ras activates MAP kinase.
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1. Active Ras recruits MAP KKK (Raf)
2. Raf releases inhibitory complexes 3. GTP hydrolyzed 4. Thus releasing active Raf. 5. Raf binds to and phosphorylates MAP KK (MEK) 6. MEK phosphorylates MAP kinase ona threonine and tyrosine residue. |
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What is the activation criteria for MAP kinase in terms of phosphorylation?
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Both threonine and tyrosine residues must be phosphorylated.
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What does MAP K do once it is active?
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Dimerizes and translocates to nucleus where it will phosphorylate TCR TF
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Once in the nucleus, what does MAP K phosphorylate?
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TCF transcription factor
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What does TCF transcription factor do once it is activated?
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Associates with SRF
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TCF/SRF complex bind to genes containing what?
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SRE (Serum Response Elements)
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What does SRE (Serum Response Elements) do?
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Allow for cell proliferation by activating transcription (such as Cyclin D for cell cycle)
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RTK's are teminated by what two things?
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1. Protein phosphatases
2. Endocytosis |
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What is the strongest growth promoting signal in breast CA?
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Her-2
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Over-amplification of Her-2 is a recognized marker for what
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Poor survival of pts. with node positive breast CA
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Do moderately positive breast tumors have HER2 gene amplification?
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No. Only those with intense tumors
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What is Erb-B?
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RTK receptor family associated with breast cancer.
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What is the function of FTI (Farnesyltransferase Inhibitor)?
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To inhibit activity of Ras in tumors
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How does FTI work?
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Ras needs to bind to PM to have activity, but FTI adds C15-farnesyl to Ras fucking up its ability to membrane target.
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