| First Author | Rovira-Clavé X | Year | 2016 |
| Journal | J Leukoc Biol | Volume | 99 |
| Issue | 1 | Pages | 143-52 |
| PubMed ID | 26302753 | Mgi Jnum | J:242872 |
| Mgi Id | MGI:5906977 | Doi | 10.1189/jlb.2A0115-034R |
| Citation | Rovira-Clave X, et al. (2016) Dual role of ERK5 in the regulation of T cell receptor expression at the T cell surface. J Leukoc Biol 99(1):143-52 |
| abstractText | Regulation of the levels of the TCR/CD3 complex at the cell surface is critical to proper T cell development and mature T cell activation. We provide evidence that the MAPK ERK5 regulates the surface expression of the TCR/CD3 complex by controlling the degradation of the CD3zeta chain and the recovery of the complex after anti-CD3epsilon stimulation. ERK5 knockdown led to TCR/CD3 up-regulation at the cell surface and increased amounts of the CD3zeta chain. Inhibition of the MEK5-dependent phosphorylation status of the kinase domain of ERK5 in human T CD4(+) cells reduced CD3zeta ubiquitination and degradation, limiting TCR/CD3 down-regulation in anti-CD3-stimulated cells. Moreover, TCR/CD3 recovery at the cell surface, after anti-CD3epsilon treatment, is impaired by ERK5 knockdown or pharmacological inhibition of autophosphorylation in the ERK5 C-terminal region. ERK5 loss in thymocytes augmented cellular CD3zeta and increased cell surface levels of TCR/CD3 on CD4(+)CD8(+) thymocytes. This correlated with enhanced generation of CD4(+)CD8(-)CD25(+) thymocytes. Our findings define ERK5 as a novel kinase that modulates the levels of TCR/CD3 at the cell surface by promoting CD3zeta degradation and TCR/CD3 recovery after TCR stimulation. |
