• Deutsch
Login

Open Access

  • Home
  • Search
  • Browse
  • Publish
  • FAQ

Refine

Author

  • Lovatt, Matt (1)
  • Maqueira-Iglesias, Braudel (1)
  • Raab, Monika (1)
  • Rudd, Christopher E. (1)
  • Schneider, Helga (1)
  • Smith, Xin (1)
  • Strebhardt, Klaus (1)
  • Valk, Elke (1)
  • Wang, Hongyan (1)
  • Wu, Zhonglin (1)
+ more

Year of publication

  • 2008 (1)

Document Type

  • Article (1)

Language

  • English (1)

Has Fulltext

  • yes (1)

Is part of the Bibliography

  • no (1) (remove)

Institute

  • Medizin (1)

1 search hit

  • 1 to 1
  • 10
  • 20
  • 50
  • 100
Adaptor SKAP-55 binds p21ras activating exchange factor RasGRP1 and negatively regulates the p21ras-ERK pathway in T-Cells (2008)
Schneider, Helga ; Wang, Hongyan ; Raab, Monika ; Valk, Elke ; Smith, Xin ; Lovatt, Matt ; Wu, Zhonglin ; Maqueira-Iglesias, Braudel ; Strebhardt, Klaus ; Rudd, Christopher E.
While the adaptor SKAP-55 mediates LFA-1 adhesion on T-cells, it is not known whether the adaptor regulates other aspects of signaling. SKAP-55 could potentially act as a node to coordinate the modulation of adhesion with downstream signaling. In this regard, the GTPase p21ras and the extracellular signal-regulated kinase (ERK) pathway play central roles in T-cell function. In this study, we report that SKAP-55 has opposing effects on adhesion and the activation of the p21ras -ERK pathway in T-cells. SKAP-55 deficient primary T-cells showed a defect in LFA-1 adhesion concurrent with the hyper-activation of the ERK pathway relative to wild-type cells. RNAi knock down (KD) of SKAP-55 in T-cell lines also showed an increase in p21ras activation, while over-expression of SKAP-55 inhibited activation of ERK and its transcriptional target ELK. Three observations implicated the p21ras activating exchange factor RasGRP1 in the process. Firstly, SKAP-55 bound to RasGRP1 via its C-terminus, while secondly, the loss of binding abrogated SKAP-55 inhibition of ERK and ELK activation. Thirdly, SKAP-55−/− primary T-cells showed an increased presence of RasGRP1 in the trans-Golgi network (TGN) following TCR activation, the site where p21ras becomes activated. Our findings indicate that SKAP-55 has a dual role in regulating p21ras-ERK pathway via RasGRP1, as a possible mechanism to restrict activation during T-cell adhesion.
  • 1 to 1

OPUS4 Logo

  • Contact
  • Imprint
  • Sitelinks