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An alternative mode of CD 43 signal transduction activates pro‐survival pathways of T lymphocytes
Author(s) -
BravoAdame Maria Elena,
VeraEstrella Rosario,
Barkla Bronwyn J.,
MartínezCampos Cecilia,
FloresAlcantar Angel,
OcelotlOviedo Jose Pablo,
PedrazaAlva Gustavo,
Rosenstein Yvonne
Publication year - 2017
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12670
Subject(s) - signal transduction , microbiology and biotechnology , biology , creb , phosphorylation , protein kinase c , kinase , pkm2 , glycolysis , pyruvate kinase , biochemistry , transcription factor , enzyme , gene
Summary CD 43 is one of the most abundant co‐stimulatory molecules on a T‐cell surface; it transduces activation signals through its cytoplasmic domain, contributing to modulation of the outcome of T‐cell responses. The aim of this study was to uncover new signalling pathways regulated by this sialomucin. Analysis of changes in protein abundance allowed us to identify pyruvate kinase isozyme M2 ( PKM 2), an enzyme of the glycolytic pathway, as an element potentially participating in the signalling cascade resulting from the engagement of CD 43 and the T‐cell receptor ( TCR ). We found that the glycolytic activity of this enzyme was not significantly increased in response to TCR + CD 43 co‐stimulation, but that PKM 2 was tyrosine phosphorylated, suggesting that it was performing moonlight functions. We report that phosphorylation of both Y 105 of PKM 2 and of Y 705 of signal transducer and activator of transcription 3 was induced in response to TCR + CD 43 co‐stimulation, resulting in activation of the mitogen‐activated protein kinase kinase 5/extracellular signal‐regulated kinase 5 ( MEK 5/ ERK 5) pathway. ERK 5 and the cAMP response element binding protein ( CREB ) were activated, and c‐Myc and nuclear factor‐ κ B (p65) nuclear localization, as well as Bad phosphorylation, were augmented. Consistent with this, expression of human CD 43 in a murine T‐cell hybridoma favoured cell survival. Altogether, our data highlight novel signalling pathways for the CD 43 molecule in T lymphocytes, and underscore a role for CD 43 in promoting cell survival through non‐glycolytic functions of metabolic enzymes.