Glypican-3
Glypican-3 (GPC3) is a GPI-anchored cell surface heparan sulfate proteoglycan that modulates hedgehog, Wnt and BMP signalling. It is also known as OCI-5, SGBS, SGBS1, SGB, DGSX and SDYS, and belongs to the glypican family. Browse Assay Genie's current range of Glypican-3 research reagents below, or read on for the biology behind the target.
Glypican-3 is a cell surface proteoglycan that acts as a signalling regulator. Attached to the membrane through its GPI anchor, it negatively regulates the hedgehog pathway by competing with the hedgehog receptor PTC1 for binding to hedgehog proteins. Binding to SHH triggers internalisation of the complex by endocytosis and its subsequent lysosomal degradation. In contrast, Glypican-3 positively regulates canonical Wnt signalling by binding the Wnt receptor Frizzled and stimulating its binding to Wnt ligands, and it also promotes non-canonical Wnt signalling.
Glypican-3 has several further reported activities. It binds CD81, reducing the free CD81 available to bind the transcriptional repressor HHEX, which leads to HHEX nuclear translocation and transcriptional repression. It inhibits the dipeptidyl peptidase activity of DPP4 (also called CD26), and it can induce apoptosis in certain cell types. In development, it controls the cellular response to BMP4 in limb patterning and skeletal development, modulates the effects of BMP2, BMP7 and FGF7 on renal branching morphogenesis, is required for coronary vascular development, and helps regulate cell movements during gastrulation.
Cell surface heparan sulfate proteoglycans consist of a membrane-associated core protein carrying a variable number of heparan sulfate chains. Members of the glypican-related integral membrane proteoglycan family, which are tethered by a glycosyl phosphatidylinositol linkage, may contribute to the control of cell division and growth regulation. The human GPC3 gene undergoes alternative splicing to give multiple transcript variants, and deletion mutations in it are associated with Simpson-Golabi-Behmel syndrome, also known as Simpson dysmorphia syndrome. Mouse and rat both carry a Gpc3 ortholog.
Glypican-3 competes with PTC1 for hedgehog binding and drives SHH internalisation and lysosomal degradation, making it a tool for studying pathway attenuation.
By binding Frizzled and promoting Wnt ligand engagement, Glypican-3 positively regulates both canonical and non-canonical Wnt signalling.
Glypican-3 influences BMP4 responses, limb and skeletal patterning, renal branching morphogenesis, coronary vascular development and gastrulation movements.
Deletion mutations in GPC3 are associated with Simpson-Golabi-Behmel syndrome, linking the protein to growth regulation and developmental disorders.
Glypican-3 is a GPI-anchored cell surface proteoglycan that negatively regulates hedgehog signalling and positively regulates Wnt signalling. It also binds CD81, inhibits DPP4 activity and shapes BMP4, BMP2, BMP7 and FGF7 responses during development.
The GPC3 gene has also been called OCI-5, SGBS, SGBS1, SGB, DGSX and SDYS. Alternative splicing produces multiple transcript variants, so a Glypican-3 antibody or Glypican-3 ELISA kit may recognise more than one form; check the datasheet of any product for its validated reactivity.
Deletion mutations in GPC3 are associated with Simpson-Golabi-Behmel syndrome. Orthologs exist in mouse and rat, both named Gpc3, and GPC3 belongs to the glypican family alongside GPC1, GPC2, GPC4, GPC5 and GPC6.
Other glypican family members that share the GPI-anchored heparan sulfate proteoglycan architecture.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P51654; product specifications from Assay Genie datasheets.