Two large classes of GTPase switch proteins are used in signal transduction pathways:

1. Heterotrimeric G proteins

2. Monomeric G proteins

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“canonical” Wnt signaling uses a second TM protein, LRP that associates with Frizzled in a Wnt signal– dependent manner.

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Homologs

LRP in vertebrates = Arrow in Drosophila

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In the absence of Wnts,

“free” β-catenin are targeted for degradation by a cytosolic destruction complex that is held together by the tumor suppressor protein Axin.

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β-catenin Destruction Complex contains:

Tumor suppressor APC

Dvl protein

Constitutively active protein kinases GSK 3β and CK1

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Kinases CK1 and GSK3,

sequentially phosphorylate β-catenin at multiple serine and threonine residues

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E3 βTrCP ubiquitin ligase then binds to two phosphorylated residues on β catenin, leading to ubiquitinylation and degradation in proteasomes.