Lipid Modifications of Sonic Hedgehog Ligand Dictate Cellular Reception and Signal Response

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Lipid Modifications of Sonic Hedgehog Ligand Dictate Cellular Reception and Signal Response

BACKGROUND Sonic hedgehog (Shh) signaling regulates cell growth during embryonic development, tissue homeostasis and tumorigenesis. Concentration-dependent cellular responses to secreted Shh protein are essential for tissue patterning. Shh ligand is covalently modified by two lipid moieties, cholesterol and palmitate, and their hydrophobic properties are known to govern the cellular release and...

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Cell surface reception of Sonic hedgehog (Shh) must ensure that the graded morphogenic signal is interpreted accordingly in neighboring cells to specify tissue patterns during development. Here, we report endocytic sorting signals for the receptor Patched1 (Ptch1), comprising two 'PPXY' motifs, that direct it to degradation in lysosomes. These signals are recognized by two HECT-domain ubiquitin...

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In the past two decades, the Hedgehog (HH) family of secreted proteins has been demonstrated to play an essential role in both animal development and various human diseases [1]. Sonic Hedgehog (SHH) is the most extensively studied HH protein biochemically. Fully processed SHH (SHH-Np) was previously reported to be post-translationally modified by cholesterol at its carboxyl terminus and palmiti...

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Signal dynamics in Sonic hedgehog tissue patterning.

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ژورنال

عنوان ژورنال: PLoS ONE

سال: 2011

ISSN: 1932-6203

DOI: 10.1371/journal.pone.0021353