title: Inhibition of T-cell antigen receptor signaling by overexpression of p120GAP.
abstract: T-cell antigen receptor triggering results in activation of protein kinase C and mobilization of calcium. These two signals are necessary and sufficient to activate the T-cell specific transcription factor NF-AT, which cooperates with other transcription factors activated by accessory signals to initiate expression of interleukin 2 and its receptor. The protein kinase C mediated pathway involves activation of ras proteins. In a Jurkat cell model of T-cell activation, treatment with antigen receptor agonists results in induction of expression of a reporter gene under the control of a NF-AT dependent promoter. Overexpression of the ras GTPase activating protein p120GAP in these cells caused a significant inhibition of T-cell antigen receptor mediated induction, suggesting a role for p120GAP in regulation of ras. The inhibition was overcome by expression of a valine-12 mutant ras which lacks GTPase activity.
authors.affiliation: Immunobiological Research Institute Siena, Italy.
authors.forename: C T
authors.initials: CT
authors.lastname: Baldari
authors.forename: A
authors.initials: A
authors.lastname: Heguy
authors.forename: M M
authors.initials: MM
authors.lastname: Di Somma
authors.forename: J L
authors.initials: JL
authors.lastname: Telford
mesh_terms: D020558:GTP Phosphohydrolases / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D010957:Plasmids; D016133:Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors* / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D011948:Receptors, Antigen, T-Cell; D020558:GTP Phosphohydrolases