title: GM1 inhibits early signaling events mediated by PDGF receptor in cultured human glioma cells.
abstract: Binding of platelet-derived growth factor receptor (PDGF) to its receptor (PDGFR) activates its receptor tyrosine kinase which autophosphorylates tyrosine residues. The p85 regulatory subunit of phosphatidylinositol 3-kinase (PI 3-kinase) binds to specific phosphotyrosines on PDGFR-beta and through the associated p110 catalytic subunit of PI 3-kinase catalyzes the formation of lipids that are involved in intracellular signaling. We examined if GM1 affects interactions between PDGFR-beta and specific proteins involved in PDGFR-mediated signaling. U-1242 MG cells were studied under different growth conditions using immunoprecipitation and Western Blot analysis. PDGF-stimulated the association of PDGFR-beta with p85, ras GTPase-activating protein and PLC gamma. GM1 decreased these associations in parallel with decreased tyrosine phosphorylation of PDGFR. PDGF augmented the activity of PI 3-kinase associated with PDGFR-beta, and this was attenuated by GM1. However, GM1 did not alter SH2 domains of p85. GM1 probably inhibits PDGF-induced signaling proteins with PDGFR-beta by inhibiting phosphorylation of specific tyrosines on the receptor which bind to SH2-domains on signaling proteins.
authors.affiliation: Department of Pathology, Ohio State University, Columbus 43210, USA.
authors.forename: T
authors.initials: T
authors.lastname: Farooqui
authors.forename: T
authors.initials: T
authors.lastname: Kelley
authors.forename: K M
authors.initials: KM
authors.lastname: Coggeshall
authors.forename: A A
authors.initials: AA
authors.lastname: Rampersaud
authors.forename: A J
authors.initials: AJ
authors.lastname: Yates
mesh_terms: D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D017479:Receptors, Platelet-Derived Growth Factor / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*; D014407:Tumor Cells, Cultured
chemical_list: D005677:G(M1) Ganglioside; D017479:Receptors, Platelet-Derived Growth Factor