CD5-mediated inhibition of TCR signaling proceeds normally in the absence of SHP-1

Baoxia Dong, Ally-Khan Somani, Paul E. Love, Xuan Zheng, Xiequn Chen, Jinyi Zhang

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The CD5 transmembrane glycoprotein functions as a co-receptor in the signaling pathway linking Tcell antigen receptor (TCR) engagement to activation and differentiation. Although CD5 effects on TCR signaling have been shown to be primarily inhibitory, the underlying mechanisms remain unclear. In view of recent data revealing the ability of CD5 to associate with the SHP-1 tyrosine phosphatase, a protein that also downregulates TCR signaling, we examined the role of SHP-1 in modulating CD5 function using thymocytes from SHP-1deficient viable motheaten (mev) mice. The results revealed the association of SHP-1 with CD5 to be markedly increased following TCR stimulation and indicated that this interaction was enhanced by and was dependent on CD5 tyrosine phosphorylation. However, there was no difference of the tyrosine phosphorylation status of CD5 between resting and TCR-stimulated cells in SHP-1deficient compared to wild-type thymocytes. Lack of SHP-1 activity did not affect the levels of CD5 surface expression, CD5 co-immunoprecipitable tyrosine phosphatase activity and intracellular calcium increase following co-crosslinking of the TCR and CD5. Similarly, an analysis of Tcell thymocyte populations in mev mice expressing an H-Y transgene as well as a construct mediating Tcell restricted CD5 overexpression, revealed that the reduction in the positive selection conferred by CD5 overexpression was unaffected by SHP-1 deficiency. CD5 is not a SHP-1 substrate and SHP-1 is not required for and possibly not involved in the CD5-mediated modulation of TCR signaling.

Original languageEnglish (US)
Pages (from-to)45-56
Number of pages12
JournalInternational Journal of Molecular Medicine
Volume38
Issue number1
DOIs
StatePublished - Jul 1 2016
Externally publishedYes

Fingerprint

Antigen Receptors
Thymocytes
Tyrosine
Non-Receptor Type 6 Protein Tyrosine Phosphatase
Phosphorylation
Transgenes
Phosphoric Monoester Hydrolases
Glycoproteins
Down-Regulation
Calcium
Population

Keywords

  • CD5
  • SHP-1
  • Tcell antigen receptor signalling
  • Thymic selection
  • Tyrosine phosphatise

ASJC Scopus subject areas

  • Genetics

Cite this

CD5-mediated inhibition of TCR signaling proceeds normally in the absence of SHP-1. / Dong, Baoxia; Somani, Ally-Khan; Love, Paul E.; Zheng, Xuan; Chen, Xiequn; Zhang, Jinyi.

In: International Journal of Molecular Medicine, Vol. 38, No. 1, 01.07.2016, p. 45-56.

Research output: Contribution to journalArticle

Dong, Baoxia ; Somani, Ally-Khan ; Love, Paul E. ; Zheng, Xuan ; Chen, Xiequn ; Zhang, Jinyi. / CD5-mediated inhibition of TCR signaling proceeds normally in the absence of SHP-1. In: International Journal of Molecular Medicine. 2016 ; Vol. 38, No. 1. pp. 45-56.
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