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Degradation of CLR-RAMP2 was sensitive to overexpression of hepatocyte growth factor-regulated tyrosine kinase substrate (HRS), but not to HRS knockdown, whereas CLRDelta9KR-RAMP2 degradation was unaffected. Overexpression, but not knockdown of HRS, promoted hyperubiquitination of CLR under basal conditions. These results propose a role for ubiquitin and HRS in the regulation of AM-induced degradation of CLR-RAMP2.
Results demonstrate the existence of crosstalk between beta-catenin signaling and HGS in two different types of cancer (hepatoblastoma and colorectal).
detailed analysis of the subcellular localization and functional significance of Hrs in macropinocytosis-mediated entry of Kaposi's Sarcoma-Associated Herpesvirus
ESCRT-0 protein hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) is targeted to endosomes independently of signal-transducing adaptor molecule (STAM) and the complex formation with STAM promotes its endosomal dissociation.
we identified an interaction between EsxH, which is secreted by the Esx-3 TSSS, and human hepatocyte growth factor-regulated tyrosine kinase substrate (Hgs/Hrs), a component of the endosomal sorting complex required for transport (ESCRT).
the role for tumoral c-Met expression or sMet/HGF levels as upfront selection criterion or predictive biomarkers deserve further study in this emerging area of therapeutic focus in RCC
Hrs is a regulator of endosomal cholesterol trafficking.
Hrs tyrosine phosphorylation detected upon EGF-stimulation.
These results suggested that HCV secretion from host cells requires Hrs-dependent exosomal pathway in which the viral assembly is also involved.
Hrs inhibits HIV-1 production by inhibiting citron kinase-mediated exocytosis.
ESCRT-0 component HRS is required for HIV-1 Vpu-mediated BST-2/tetherin down-regulation.
Plasma hepatocyte growth factor is associated with periampullary cancer.
hSpry2 binds to the endocytic regulatory protein, hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) and blocks intracellular signal propagation.
The HRS domain required for merlin binding is narrowed to a region (residues 470-497) containing the predicted coiled-coil domain whereas the major domain responsible for HRS growth suppression is distinct (residues 498-550).
HRS inhibits Stat3 activation in schwannoma cells.
Overexpression Hgs in T cells yielded a dose-dependent decrease in cotransfected reporter gene expression, indicating an inhibitory function of this molecule.
Data suggested that association with Hrs is a prerequisite for signal transducing adaptor molecule function.
Hrs regulates the sorting of ligand-stimulated and unstimulated growth factor receptors on early endosomes, and the FYVE domain, which is required for Hrs to reside in a microdomain of early endosomes.
the endosome-associated protein hrs is a subunit of a protein complex containing actinin-4, BERP, and myosin V that is necessary for efficient TfR recycling but not for EGFR degradation
Analysis with phospho-specific antibodies indicates that 3 kinases generate a signal-specific, combinatorial phosphorylation profile of the Hrs-STAM complex, with the potential of diversifying tyrosine kinase receptor signalling through a common element.
Findings find that Hrs is indispensable for the autophagic clearance of neurodegeneration-related proteins and for the survival of hippocampal neurons in mammals. In particular, the work provides the novel insight that the loss of Hrs results in insufficient autophagic clearance and enhanced ER stress, thereby triggering JNK activation and subsequent apoptotic and necroptotic neuronal cell death.
HGS expression in the nervous system is developmentally regulated.HGS is required for motor neuron function.
Smooth Muscle Hgs Deficiency Leads to Impaired Esophageal Motility.
These results indicate that Hrs plays important roles during peripheral development and physiological functions of B lymphocytes.
A new mechanism to modify BMP signaling by Hgs during early mouse development.
Hrs is a master molecule that controls in part the degradation of STAM1 and the accumulation of ubiquitinated proteins
Data suggest that Hrs regulates the KGFR degradative pathway, but not its juxtanuclear recycling transport, and that Hrs recruitment to the receptor, but not its ligand-induced phosphorylation, could be required for its function.
Nedd4-2 induces binding of ENaC to Hrs, which mediates the sorting decision between ENaC degradation and recycling.
Peptidergic versus nonpeptidergic specification depends on a balance between HGF-Met signaling and Runx1 extinction/maintenance in primary nociceptive neurons.
These data indicated that Hrs is involved in the regulation of antigen-presentation activity through the exosome secretion.
Src phosphorylates Hrs in vitro & in vivo. Hrs is phosphorylated in Src-, Yes- & Fyn-negative cells. 10-20% is phosphorylated after EGF stimulation at multiple tyrosines in different parts of Hrs by several kinases downstream of the EGF receptor.
Hrs, Eps15, and STAM proteins function in a multivalent complex that sorts ubiquitinated proteins into the multivesicular body pathway.
the TSG101 interaction with HRS is a crucial step in endocytic down-regulation of mitogenic signaling and this interaction may have a role in linking the functions of early and late endosomes
Our results suggest that GEF-1 may induce MDCK and C3H10T1/2 cells to trans-differentiate into myoblast-like cells.
the Hrs hexamer interacts with the membrane and acts as a "master molecule" that presents multiple sites for protein binding
In structure-function studies of Cbl and EGFR mutants, the level of Hrs phosphorylation and rapidity of apparent Hrs dephosphorylation correlated directly with EGFR degradation.
The restoration of Hrs expression increased cell proliferation and anchorage-independent growth in a mouse embryonic fibroblast line established from a Hrs knockout mouse.
These data suggest that Hrs plays an important role in neural cell survival in vivo and provide an animal model for neurodegenerative diseases that are known to be commonly affected by the generation of proteinaceous aggregates.
The protein encoded by this gene regulates endosomal sorting and plays a critical role in the recycling and degradation of membrane receptors. The encoded protein sorts monoubiquitinated membrane proteins into the multivesicular body, targeting these proteins for lysosome-dependent degradation.
human growth factor-regulated tyrosine kinase substrate
, protein pp110
, HGF-regulated tyrosine kinase substrate
, SNAP-25-interacting protein Hrs-2
, hepatoCyte growth factor receptor
, hepatocyte growth factor-regulated tyrosine kinase substrate