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Vertebrate muscle differentiation is coordinated by an intricate network of transcription factors requiring proliferating myogenic precursors to withdraw irreversibly from the cell cycle. Recent studies have implicated a large number of microRNAs exerting another layer of control in many aspects of muscle differentiation. By annealing to short recognition(More)
Rhabdomyosarcoma (RMS) is a childhood malignant soft tissue cancer that is derived from myogenic progenitors trapped in a permanent mode of growth. Here, we report that miR-214 is markedly down-regulated in human RMS cell lines. Although not required for embryogenesis in mice, miR-214 suppresses mouse embryonic fibroblast (MEF) proliferation. When(More)
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(More)
Sustained Sonic hedgehog (Shh) pathway activity is associated with tumorigenesis in a wide variety of tissues. Mutational inactivation of Shh receptor Patched (Ptch) and a downstream gene Suppressor of fused (Sufu), both of which are negative regulators of the pathway, increases susceptibility to cerebellum cancer in humans and mice. Sufu is a binding(More)
Originally identified as factors affecting Drosophila embryogenesis, the Hedgehog (Hh) pathway is one of the primary signaling systems that specify patterns of cell growth and differentiation during vertebrate development. Mutations in various components of this pathway frequently occur in tumors originated from the skin, cerebellum, and skeletal muscle,(More)
Suppressor of fused (Sufu) is an essential negative regulator of the sonic hedgehog (Shh) pathway, but little is known about how Sufu itself is normally regulated. Here, we report that Sufu is phosphorylated at Ser-342 and Ser-346 by GSK3β and cAMP-dependent protein kinase A (PKA), respectively, and phosphorylation at this dual site stabilizes Sufu against(More)
We have investigated whether transmembrane amino acid residues Asp128 (domain III), Tyr129 (domain III) [corrected], and Tyr308 (domain VII) in the mouse delta opioid receptor play a role in receptor activation. To do so, we have used a [35S]GTPgammaS (where GTPgammaS is guanosine 5'-3-O-(thio)triphosphate) binding assay to quantify the activation of(More)
Gastric cancer is one of the leading causes of cancer death world-wide and carries a high rate of metastatic risk. In addition to other protein-coding oncogenes and tumor suppressor genes, microRNAs play an important role in gastric cancer tumorigenic progression. Here, we show that miR-206 is expressed at markedly low levels in a cohort of gastric tumors(More)
Suppressor of fused (Sufu) is an essential negative regulator of the Sonic hedgehog (Shh) pathway, but little is known about how Sufu itself is normally regulated. Here, we report that Sufu is phosphorylated at S342 and S346 by GSK3β and cAMP-dependent protein kinase A (PKA), respectively, and phosphorylation at this dual site stabilizes Sufu against Shh(More)
OBJECTIVE The di-leucine motif exists in the intracellular domains of certain cell surface receptors, participating in the receptor-mediated endocytosis. The present study was aimed at determining the role of the di-leucine motif in class A scavenger receptor (SR-A)-mediated ligand endocytosis. METHODS AND RESULTS cDNA coding for a mutant (SR-A mutant(More)