Src homology 2 domain-containing leukocyte phosphoprotein of 76 kDa and phospholipase Cγ1 are required for NF-κB activation and lipid raft recruitment of protein kinase Cθ induced by T Cell costimulation

• Verfasst von: Dienz, Oliver [VerfasserIn]
• Verfasst von: Krammer, Peter H. [VerfasserIn]
• Titel: Src homology 2 domain-containing leukocyte phosphoprotein of 76 kDa and phospholipase Cγ1 are required for NF-κB activation and lipid raft recruitment of protein kinase Cθ induced by T Cell costimulation
• Verf.angabe: Oliver Dienz, Andreas Möller, Andreas Strecker, Nadja Stephan, Peter H. Krammer, Wulf Dröge, and M. Lienhard Schmitz
• E-Jahr: 2003
• Jahr: January 1, 2003
• Umfang: 8 S.
• Teil: volume:170
• Teil: year:2003
• Teil: number:1
• Teil: pages:365-372
• Teil: extent:8
• Fussnoten: Gesehen am 08.04.2021
• Titel Quelle: Enthalten in: The journal of immunology
• Ort Quelle: Bethesda, Md. : Soc., 1916
• Jahr Quelle: 2003
• Band/Heft Quelle: 170(2003), 1, Seite 365-372
• ISSN Quelle: 1550-6606
• DOI: doi:10.4049/jimmunol.170.1.365
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1753373778

Abstract

The NF-κB activation pathway induced by T cell costimulation uses various molecules including Vav1 and protein kinase C (PKC)θ. Because Vav1 inducibly associates with further proteins including phospholipase C (PLC)γ1 and Src homology 2 domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76), we investigated their role for NF-κB activation in Jurkat leukemia T cell lines deficient for expression of these two proteins. Cells lacking SLP-76 or PLCγ1 failed to activate NF-κB in response to T cell costimulation. In contrast, replenishment of SLP-76 or PLCγ1 expression restored CD3/CD28-induced IκB kinase (IKK) activity as well as NF-κB DNA binding and transactivation. PKCθ activated NF-κB in SLP-76- and PLCγ1-deficient cells, showing that PKCθ is acting further downstream. In contrast, Vav1-induced NF-κB activation was normal in SLP-76− cells, but absent in PLCγ1− cells. CD3/CD28-stimulated recruitment of PKCθ and IKKγ to lipid rafts was lost in SLP-76- or PLCγ1-negative cells, while translocation of Vav1 remained unaffected. Accordingly, recruitment of PKCθ to the immunological synapse strictly relied on the presence of SLP-76 and PLCγ1, but synapse translocation of Vav1 identified in this study was independent from both proteins. These results show the importance of SLP-76 and PLCγ1 for NF-κB activation and raft translocation of PKCθ and IKKγ.