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223.22 Enzyme Linked Receptors
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2015-11-22
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Cell Biology Lecture 223.22: Enzyme-Linked Protein Receptors
Enzyme Linked Receptors
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Enzyme Linked Receptors
Enzyme Linked Receptors
• Transmembrane Guanylate Cyclases
• Receptor Tyrosine Phosphatases
• Transmembrane Serine/Threonine Kinases
• Receptor Tyrosine Kinase Associated Receptors
• Receptor Tyrosine Kinases
5 FAMILIES OF ENZYME-LINKED RECEPTORS
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Receptor tyrosine kinases
Enzyme Linked Receptors
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Enzyme Linked Receptors
SH2 - Link protein to receptor
SH3 - Links protein to downstream events
PI 3-kinase has both SH2 and SH3 domains allowing it to bind the activated RTK and link to other signalling proteins
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Enzyme Linked Receptors
SH2 - Link protein to receptor
SH3 - Links protein to downstream events
REVIEW: G-Protein Linked Receptors and Ca 2+
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Enzyme Linked Receptors
Enzyme Linked Receptors
SH2 - Link protein to receptor
SH3 - Links protein to downstream events
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SH2 - Link protein to receptor
SH3 - Links protein to downstream events
Enzyme Linked Receptors
(aka Guanine nucleotide exchange factor = GEF)
GTPase activating protein (GAP)
deactivates this
Enzyme Linked Receptors
Guanosine nucleotide exchange factor (GEF) = Ras Activating Protein (RAP)
GTPase activating protein (GAP) Activator
Bind RTK indirectly Deactivator Bind RTK directly
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Enzyme Linked Receptors
MAPKKK
MAPKK
MAPK – only fully activated when phosphorylated on a
threonine and tyrosine residue
McDonald P. C., Oloumi A., Mills J., Dobreva I., Maidan M., Gray V., Wederell E. D., Bally M. B., Foster L. J., and Dedhar S. (2008) Rictor and Integrin-Linked Kinase Interact and Regulate AKT Phosphorylation and Cancer Cell Survival. Cancer Res. 68, 1618-1624. Links ILK to the Tor complex, a target for the anticancer drug rapamycin.
RTK activates the PI-3-kinase AKT signalling pathway. AKT stimulates cells to grow in size by activating Tor. Tor and its associated proteins are anticancer drug targets
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i.e., If block signaling at X, can you rescue the effect with overactive Ras? This would indicate that Ras is downstream from X in the signalling pathway.
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