Format:
Online-Ressource
ISSN:
1521-4141
Content:
Abstract: T lymphocyte activation is controlled by a coordinated web of tyrosine and serine kinases. There is a large body of information about tyrosine kinase substrates in T cells but analysis of serine kinase substrates has been more difficult. Recently we described an antiserum that recognizes serine‐phosphorylated peptides corresponding to the substrate sequences for AGC serine kinases. This antiserum, termed PAP‐1 (phospho antibody for proteomics‐1), has proven useful for probing the serine phosphoproteome of antigen receptor‐activated T lymphocytes. The present study shows that PAP‐1 can also be used to explore serine kinases activated by cytokines and chemokines in T cells. Using PAP‐1, together with proteomic analysis, the precursor form of the cytokine IL‐16 (ProIL‐16) was shown to be phosphorylated on Ser144 in antigen receptor‐, SDF1α‐ and IL‐2‐activated T cells. Genetic and pharmacological‐inhibitor experiments showed that the phosphorylation of ProIL‐16 is dependent on activation of the kinases Erk1/2. IL‐16 is secreted by mitogen‐activated T cells, and the biochemical link between ProIL‐16 and Erk1/2, revealed by studies with PAP‐1, prompted analysis of the role of MAP kinases in this response. We show that TCR‐mediated secretion of IL‐16 is dependent on MAP kinases. The present study thus reveals how phosphoproteomic analysis opens previously unrecognized avenues for research, and yields novel insights about targets for MAP kinases in T lymphocytes.
In:
volume:34
In:
number:2
In:
year:2004
In:
pages:587-597
In:
extent:11
In:
European journal of immunology, Weinheim : Wiley-VCH, 1971-, 34, Heft 2 (2004), 587-597 (gesamt 11), 1521-4141
Language:
English
DOI:
10.1002/eji.200324598
URN:
urn:nbn:de:101:1-2023100107031612441628
URL:
https://doi.org/10.1002/eji.200324598
URL:
https://nbn-resolving.org/urn:nbn:de:101:1-2023100107031612441628
URL:
https://d-nb.info/1304629287/34
URL:
https://doi.org/10.1002/eji.200324598
Bookmarklink