Role of Patched-1 Intracellular Domains in Canonical and Non-Canonical Hedgehog Signalling Events
Patched-1 (Ptch1) is the primary receptor for Hedgehog (Hh) ligands and mediates both canonical and non-canonical Hh signalling. Previously, our lab identified that mice possessing a Ptch1 C-terminal truncation display blocked mammary gland development at puberty that is overcome by overexpression o...
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ndltd-LACETR-oai-collectionscanada.gc.ca-OTU.1807-428772013-12-06T03:37:54ZRole of Patched-1 Intracellular Domains in Canonical and Non-Canonical Hedgehog Signalling EventsHarvey, MalcolmHedgehog signallingMolecular Biology0307Patched-1 (Ptch1) is the primary receptor for Hedgehog (Hh) ligands and mediates both canonical and non-canonical Hh signalling. Previously, our lab identified that mice possessing a Ptch1 C-terminal truncation display blocked mammary gland development at puberty that is overcome by overexpression of activated c-src. Testing the hypothesis that this involves a direct interaction between Ptch1 and c-src, we identified through co-immunoprecipitation that Ptch1 and c-src associate in an Hh-dependent manner, and that the Ptch1 C-terminus regulates activation of c-src in response to Hh ligand. Since the effects of Ptch1 intracellular domain deletions on canonical Hh signalling are ill-defined, we assayed this through luciferase reporter assays and qRT-PCR. Transient assays revealed that the Ptch1 middle intracellular loop is required for response to ligand, while qRT-PCR from primary cells showed that C-terminal truncation impairs canonical Ptch1 function. Together, this indicates that the intracellular domains of Ptch1 mediate distinct canonical and non-canonical functions.Hamel, Paul A.2013-112013-11-27T15:26:22ZNO_RESTRICTION2013-11-27T15:26:22Z2013-11-27Thesishttp://hdl.handle.net/1807/42877en_ca |
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Hedgehog signalling Molecular Biology 0307 |
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Hedgehog signalling Molecular Biology 0307 Harvey, Malcolm Role of Patched-1 Intracellular Domains in Canonical and Non-Canonical Hedgehog Signalling Events |
description |
Patched-1 (Ptch1) is the primary receptor for Hedgehog (Hh) ligands and mediates both canonical and non-canonical Hh signalling. Previously, our lab identified that mice possessing a Ptch1 C-terminal truncation display blocked mammary gland development at puberty that is overcome by overexpression of activated c-src. Testing the hypothesis that this involves a direct interaction between Ptch1 and c-src, we identified through co-immunoprecipitation that Ptch1 and c-src associate in an Hh-dependent manner, and that the Ptch1 C-terminus regulates activation of c-src in response to Hh ligand. Since the effects of Ptch1 intracellular domain deletions on canonical Hh signalling are ill-defined, we assayed this through luciferase reporter assays and qRT-PCR. Transient assays revealed that the Ptch1 middle intracellular loop is required for response to ligand, while qRT-PCR from primary cells showed that C-terminal truncation impairs canonical Ptch1 function. Together, this indicates that the intracellular domains of Ptch1 mediate distinct canonical and non-canonical functions. |
author2 |
Hamel, Paul A. |
author_facet |
Hamel, Paul A. Harvey, Malcolm |
author |
Harvey, Malcolm |
author_sort |
Harvey, Malcolm |
title |
Role of Patched-1 Intracellular Domains in Canonical and Non-Canonical Hedgehog Signalling Events |
title_short |
Role of Patched-1 Intracellular Domains in Canonical and Non-Canonical Hedgehog Signalling Events |
title_full |
Role of Patched-1 Intracellular Domains in Canonical and Non-Canonical Hedgehog Signalling Events |
title_fullStr |
Role of Patched-1 Intracellular Domains in Canonical and Non-Canonical Hedgehog Signalling Events |
title_full_unstemmed |
Role of Patched-1 Intracellular Domains in Canonical and Non-Canonical Hedgehog Signalling Events |
title_sort |
role of patched-1 intracellular domains in canonical and non-canonical hedgehog signalling events |
publishDate |
2013 |
url |
http://hdl.handle.net/1807/42877 |
work_keys_str_mv |
AT harveymalcolm roleofpatched1intracellulardomainsincanonicalandnoncanonicalhedgehogsignallingevents |
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1716616388776296448 |