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A PKA inhibitor motif within SMOOTHENED controls Hedgehog signal transduction - Nature Structural & Molecular Biology

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A PKA inhibitor motif within SMOOTHENED controls Hedgehog signal transduction - Nature Structural & Molecular Biology

The Hedgehog (Hh) cascade is central to development, tissue homeostasis and cancer. A pivotal step in Hh signal transduction is the activation of glioma-associated (GLI) transcription factors by the atypical G protein-coupled receptor (GPCR) SMOOTHENED (SMO). How SMO activates GLI remains unclear. Here we show that SMO uses a decoy substrate sequence to physically block the active site of the cAMP-dependent protein kinase (PKA) catalytic subunit (PKA-C) and extinguish its enzymatic activity.

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A PKA inhibitor motif within SMOOTHENED controls Hedgehog signal transduction - Nature Structural & Molecular Biology

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A PKA inhibitor motif within SMOOTHENED controls Hedgehog signal transduction - Nature Structural & Molecular Biology

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