An alternative mode of CD43 signal transduction activates pro-survival pathways of T lymphocytes.
CD43 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 (PKM2), an enzyme of the glycolytic pathway, as an element potentially participating in the signalling cascade resulting from the engagement of CD43 and the T-cell receptor (TCR). We found that the glycolytic activity of this enzyme was not significantly increased in response to TCR+CD43 co-stimulation, but that PKM2 was tyrosine phosphorylated, suggesting that it was performing moonlight functions. We report that phosphorylation of both Y105of PKM2 and of Y705of signal transducer and activator of transcription 3 was induced in response to TCR+CD43 co-stimulation, resulting in activation of the mitogen-activated protein kinase kinase 5/extracellular signal-regulated kinase 5 (MEK5/ERK5) pathway. ERK5 and the cAMP response element binding protein (CREB) were activated, and c-Myc and nuclear factor-κB (p65) nuclear localization, as well as Bad phosphorylation, were augmented. Consistent with this, expression of human CD43 in a murine T-cell hybridoma favoured cell survival. Altogether, our data highlight novel signalling pathways for the CD43 molecule in T lymphocytes, and underscore a role for CD43 in promoting cell survival through non-glycolytic functions of metabolic enzymes.
Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, México.|Posgrado en Ciencias Bioquímicas, UNAM, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, México.
Maria Elena
ME
Bravo-Adame
Departamento de Biología Molecular de Plantas, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, México.
Rosario
R
Vera-Estrella
Southern Cross Plant Science, Southern Cross University, Lismore, NSW, Australia.
Bronwyn J
http://orcid.org/0000-0002-4691-8023
BJ
Barkla
Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, México.|Posgrado en Ciencias Bioquímicas, UNAM, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, México.
Cecilia
C
Martínez-Campos
Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, México.
Angel
A
Flores-Alcantar
Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, México.
Jose Pablo
JP
Ocelotl-Oviedo
Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, México.
Gustavo
G
Pedraza-Alva
Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, México.
Yvonne
Y
Rosenstein
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002470:Cell Survival; D006801:Humans; D006825:Hybridomas; D007111:Immunity, Cellular; D019169:Jurkat Cells; D051917:Leukosialin / Q000378:metabolism*; D008213:Lymphocyte Activation; D048671:MAP Kinase Kinase 5 / Q000378:metabolism; D051379:Mice; D048054:Mitogen-Activated Protein Kinase 7 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D011770:Pyruvate Kinase / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D051917:Leukosialin; C489427:MYC protein, human; D016328:NF-kappa B; D016271:Proto-Oncogene Proteins c-myc; D050796:STAT3 Transcription Factor; D011770:Pyruvate Kinase; D048054:Mitogen-Activated Protein Kinase 7; D048671:MAP Kinase Kinase 5; C482563:MAP2K5 protein, human
CD43; T-cell survival; cAMP response element binding protein signalling; extracellular signal-regulated kinase 5; pyruvate kinase isoform M2