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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.