4.5 Article

T-cell receptor early signalling complex activation in response to interferon-α receptor stimulation

Journal

BIOCHEMICAL JOURNAL
Volume 428, Issue -, Pages 429-437

Publisher

PORTLAND PRESS LTD
DOI: 10.1042/BJ20091660

Keywords

interferon-alpha receptor (IFN alpha R); Janus kinase/signal transducer and activator of transcription pathway (JAK/STAT pathway); mitogen-activated protein kinase pathway (MAPK pathway); Slp76; T-cell receptor early signalling complex (TCR ESC); Vav

Funding

  1. Wellcome Trust [054191]
  2. U.K. Biotechnology and Biological Sciences Research Council
  3. Associazione Italiana per la Ricerca sul Cancro
  4. U.K. Medical Research Council [G0400197]
  5. MRC [G0400197] Funding Source: UKRI
  6. Medical Research Council [G0400197] Funding Source: researchfish

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Signalling through the IFN alpha R (interferon-alpha receptor) and TCR (T-cell receptor) in Jurkat T lymphocytes results in distinct immune responses. Despite this both receptors elicit ERK (extracellular-signal-regulated kinase)/MAPK (mitogen-activated protein kinase) phosphorylation. Vav and Slp76 are shown to be required for IFN alpha (interferon-alpha)-stimulated ERK activity. These form a subset of proteins which behave identically on stimulation of both receptors. TCR deletion abrogates IFN alpha R-stimulated MAPK activity, whereas the canonical JAK/STAT (Janus kinase/signal transducer and activator of transcription) pathway is unaffected. Thus recruitment of the intact TCR ESC (early signalling complex) is necessary for this downstream MAPK response. Despite using a common ESC, stimulation of the IFN alpha R does not produce the transcriptional response associated with TCR. Up-regulation of the MAPK pathway by IFN alpha R might be important to ensure that the cell responds to only one stimulant.

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