IL-12-dependent activation of ERK1/2 in human T lymphoblasts.
According to some authors, membrane compartmentalization is a key regulator of CD45 function. Indeed, it has been described that CD45 repositioning from raft microdomains to phospholipid-rich plasma membrane areas leads to the activation of extracellular signal-regulated kinases (ERKs). We have previously shown that interleukin-12 (IL-12) increases the expression of CD26, promoting the interaction of CD26 with CD45R0 (a CD45 isoform) and removing CD45R0 from lipid rafts. Thus, this IL-12-dependent removal of CD45RO from rafts could, hypothetically, fulfill functions like the activation of the ERK1/2 pathway. IL-12 is an important interleukin for T cells. Upon interaction with its receptor (interleukin-12 receptor; IL-12R), this cytokine triggers a signalling cascade, where the classical Janus kinase (JAK)-signal transducers and activators of transcription (STAT) pathway and other additional routes participate. Due to the promitogenic effect of IL-12 and the influence of this cytokine on CD45RO compartmentalization, ERK kinases were likely candidates to be downstream of IL-12R. However, several research groups have rejected a role for these kinases. Now, results in this paper show that the IL-12R binding, similar to the stimulation via T cell receptor (TCR), promotes the activation of the Raf/MEK-1/ERK1/2 pathway. In addition, the IL-12R-associated Janus kinase JAK2, but not TYK2, seems upstream of this important pathway for the proliferation of human T cells. However, even though c-Myc is slightly up-regulated by IL-12 and partially mediates the proliferative effect of IL-12, this transcription factor was not found downstream of ERK1/2.
Canda-Sánchez
Ana
A
Department of Biochemistry and Molecular Biology, CIBUS, University of Santiago de Compostela, C/Lope Gómez de Marzoa s/n, 15782 Santiago de Compostela, A Coruña, Spain.
Salgado
Francisco J
FJ
Pérez-Díaz
Amparo
A
Varela-González
Carla
C
Arias
Pilar
P
Nogueira
Montserrat
M
D049109:Cell Proliferation; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism*; D053614:Janus Kinase 2 / Q000276:immunology / Q000378:metabolism*; D017493:Leukocyte Common Antigens; D008213:Lymphocyte Activation / Q000187:drug effects; D010835:Phytohemagglutinins / Q000276:immunology; D021122:Protein Subunits / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D053707:Receptors, Interleukin-12 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D020032:Tyrphostins / Q000494:pharmacology
D010835:Phytohemagglutinins; D021122:Protein Subunits; D053707:Receptors, Interleukin-12; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D018664:Interleukin-12; D007371:Interferon-gamma; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D017493:Leukocyte Common Antigens