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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

5 FAMILIES OF ENZYME-LINKED RECEPTORS

Transmembrane Guanylate Cyclases

Receptor Tyrosine Phosphatases
Transmembrane Serine/Threonine Kinases
Receptor Tyrosine Kinase Associated
Receptors
Receptor Tyrosine Kinases

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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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Enzyme Linked Receptors

GTPase activating
protein (GAP)
deactivates this
(aka Guanine nucleotide exchange factor = GEF)

SH2 - Link protein to receptor

SH3 - Links protein to downstream events

Enzyme Linked Receptors

Guanosine nucleotide
exchange factor (GEF) = Ras
Activating Protein (RAP)

GTPase activating
protein (GAP)

Deactivator
Bind RTK directly

Activator
Bind RTK indirectly

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Enzyme Linked Receptors

MAPKKK

MAPKK
MAPK only fully activated
when phosphorylated on a
threonine and tyrosine residue

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

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.

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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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