Characterization of TCR-induced receptor-proximal signaling events negatively regulated by the protein tyrosine phosphatase PEP

Anette Gjörloff-Wingren, Manju Saxena, Scott Williams, Don Hammi, Tomas Mustelin

Forskningsoutput: TidskriftsbidragArtikelPeer review

165 Citeringar (Scopus)

Sammanfattning

The proline-, glutamic acid-, serine- and threonine-enriched protein tyrosine phosphatase PEP, which is expressed primarily in hematopoietic cells, was recently discovered to be physically associated with the 50-kDa cytosolic protein tyrosine kinase (PTK) Csk, an important suppressor of Src family PTK, including Lck and Fyn in T cells. We report that this phos phatase has an inhibitory effect on TCR-induced transcriptional activation of the c-fos protooncogene and elements from the IL-2 gene promoter. Catalytically inactive mutants of PEP had no effects in these assays. Expression of PEP also reduced activation of the N-terminal c-jun kinase Jnk2 in response to receptor ligation, but not in response to UV light. In agreement with a more receptor-proximal site of action, we found that PEP reduced the TCR-induced increase in tyrosine phosphorylation of an Lck mutant, Lck-Y505F, which is only phosphorylated on tyrosine 394, the positive regulatory site. Finally, we observed that PEP reduced c-fos activation in a synergisitic manner with Csk, supporting the notion that these two enzymes form a functional team acting on Src family kinases involved in TCR signaling.

OriginalspråkEngelska
Sidor (från-till)3845-3854
Antal sidor10
TidskriftEuropean Journal of Immunology
Volym29
Nummer12
DOI
StatusPublicerad - 1999
Externt publiceradJa

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  • Biologi (106)

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