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1996 1
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1998 9
1999 15
2000 11
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2002 22
2003 26
2004 22
2005 22
2006 33
2007 28
2008 25
2009 38
2010 26
2011 34
2012 37
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2018 12
2019 7
2020 0
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Page 1
The protein-specific activities of the transmembrane modules of Ptch1 and Ptch2 are determined by their adjacent protein domains.
Fleet AJ and Hamel PA. J Biol Chem 2018. PMID 30166346 Free PMC article.
However, the SSD of Ptch2 were capable of repressing Hh signaling, as determined using chimeric proteins where the SSDs of Ptch1 were replaced by those from Ptch2. Replacement of the SSDs of Ptch1 with the analogous regions from the cholesterol transporter NPC1 failed to produce a chimeric protein capable of Hh repression. ...
However, the SSD of Ptch2 were capable of repressing Hh signaling, as determined using chimeric proteins where the SSDs of Ptch1
Genetic ablation of Gpr37l1 delays tumor occurrence in Ptch1(+/-) mouse models of medulloblastoma.
Di Pietro C, et al. Exp Neurol 2019. PMID 30452905
The G-protein coupled receptor 37-like 1 (Gpr37l1) is specifically expressed in most astrocytic glial cells, including cerebellar Bergmann astrocytes and interacts with patched 1 (Ptch1), a co-receptor of the sonic hedgehog (Shh)-smoothened (Smo) signaling complex. ...It is also associated with the delayed and diminished presence of more severe types of hyperplastic lesions in Ptch1(+/-) mice. ...
The G-protein coupled receptor 37-like 1 (Gpr37l1) is specifically expressed in most astrocytic glial cells, including cerebellar Ber …
Smoothened stimulation by membrane sterols drives Hedgehog pathway activity
Deshpande I, et al. Nature 2019. PMID 31263273 Free PMC article.
Hedgehog proteins bind to and inhibit the transmembrane cholesterol transporter Patched-1 (PTCH1), which permits activation of the seven-transmembrane transducer Smoothened (SMO) via a mechanism that is poorly understood. ...Analogous to other G protein-coupled receptors, the activation of SMO is associated with subtle motions in the extracellular domain, and larger intracellular changes. ...
Hedgehog proteins bind to and inhibit the transmembrane cholesterol transporter Patched-1 (PTCH1), which permits activation of …
Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition
Kool M, et al. Cancer Cell 2014. PMID 24651015 Free PMC article.
SHH pathway mutations involved PTCH1 (across all age groups), SUFU (infants, including germline), and SMO (adults). Children >3 years old harbored an excess of downstream MYCN and GLI2 amplifications and frequent TP53 mutations, often in the germline, all of which were rare in infants and adults. Functional assays in different SHH-MB xenograft models demonstrated that SHH-MBs harboring a PTCH1 mutation were responsive to SMO inhibition, whereas tumors harboring an SUFU mutation or MYCN amplification were primarily resistant....
SHH pathway mutations involved PTCH1 (across all age groups), SUFU (infants, including germline), and SMO (adults). Children >3 ye …
Cholesterol Modification of Smoothened Is Required for Hedgehog Signaling
Xiao X, et al. Mol Cell 2017. PMID 28344083 Free article.
This modification was inhibited by Patched-1 (Ptch1) but enhanced by Hh. The SMO(D95N) mutation, which could not be cholesterol modified, was refractory to Hh-stimulated ciliary localization and failed to activate downstream signaling. ...
This modification was inhibited by Patched-1 (Ptch1) but enhanced by Hh. The SMO(D95N) mutation, which could not be cholesterol modif …
Alternative first exons of PTCH1 are differentially regulated in vivo and may confer different functions to the PTCH1 protein.
Kogerman P, et al. Oncogene 2002. PMID 12203113 Free article.
The PTCH1 gene is a human tumour suppressor gene frequently mutated in basal cell carcinoma (BCC) and several other tumour types. ...The different PTCH1 transcripts all encode proteins that interact with Smoh in doubly transfected cells. Furthermore, functional assays demonstrated that whereas all PTCH1 isoforms can inhibit the activity of SHH, only the PTCH1B isoform is capable of fully inhibiting Smoh activity. ...
The PTCH1 gene is a human tumour suppressor gene frequently mutated in basal cell carcinoma (BCC) and several other tumour types. ... …
Activation of hedgehog signaling in mesenchymal stem cells induces cartilage and bone tumor formation via Wnt/β-Catenin
Deng Q, et al. Elife 2019. PMID 31482846 Free PMC article.
Yet deletion of Ptch1, encoding an inhibitor of IHH receptor Smoothened (SMO), in chondrocyte or osteoblasts does not cause tumorigenesis. ...Moreover, Ptch1 deletion led to development of osteoarthritis-like phenotypes, exostoses, enchondroma, and osteosarcoma in Smo-Gli1/2-dependent manners. ...
Yet deletion of Ptch1, encoding an inhibitor of IHH receptor Smoothened (SMO), in chondrocyte or osteoblasts does not cause tumorigen …
Super-resolution microscopy reveals that disruption of ciliary transition-zone architecture causes Joubert syndrome
Shi X, et al. Nat Cell Biol 2017. PMID 28846093 Free PMC article.
We defined the three-dimensional arrangement of key proteins in the transition zone using two-colour stochastic optical reconstruction microscopy (STORM). ...JBTS-associated mutations in RPGRIP1L or TCTN2 displace certain transition-zone proteins. Diverse ciliary proteins accumulate at the transition zone in wild-type cells, suggesting that the transition zone is a waypoint for proteins entering and exiting the cilium. ...
We defined the three-dimensional arrangement of key proteins in the transition zone using two-colour stochastic optical reconstructio …
Identification and characterization of two novel PTCH1 splice variants.
Yu P, et al. Biochem Biophys Res Commun 2017. PMID 28390897
Exon skipping dramatically influenced the steady states of the proteins, with the levels of PTCH1-1B and PTCH1-Δ10 being significantly higher than those of PTCH1-Δ15, as detected using western blot. ...Additionally, SMO inhibition by PTCH1 occurred through a nonstoichiometric, catalytic mechanism, indicating that this inhibition was less dependent on the dose of the PTCH1 protein. ...
Exon skipping dramatically influenced the steady states of the proteins, with the levels of PTCH1-1B and PTCH1-Δ10 bein …
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