Mikel Martinez de Arbulo Echevarria

• PhD
• PostDoc Position at IIS Biogipuzkoa

Simple Summary Tyrosine phosphorylation is the first biochemical event that occurs after TCR engagement, which is crucial for T-cell development, activation and differentiation. Early TCR signals include phosphorylation events in which the tyrosine kinases Lck and ZAP70 are involved. The sequential activation of these kinases leads to the phosphory...

T lymphocytes are key players in adaptive immune responses through the recognition of peptide antigens through the T Cell Receptor (TCR). After TCR engagement, a signaling cascade is activated, leading to T cell activation, proliferation, and differentiation into effector cells. Delicate control of activation signals coupled to the TCR is needed to...

The LAT transmembrane adaptor is essential to transduce intracellular signals triggered by the TCR. Phosphorylation of its four C-terminal tyrosine residues (136, 175, 195, and 235 in mouse LAT) recruits several proteins resulting in the assembly of the LAT signalosome. Among those tyrosine residues, the one found at position 136 of mouse LAT plays...

Intracellular signaling through the T cell receptor (TCR) is essential for T cell development and function. Proper TCR signaling requires the sequential activities of Lck and ZAP-70 kinases, which result in the phosphorylation of tyrosine residues located in the CD3 ITAMs and the LAT adaptor, respectively. LAT, linker for the activation of T cells,...

The adaptor LAT plays a crucial role in the transduction of signals coming from the TCR/CD3 complex. Phosphorylation of some of its tyrosines generates recruitment sites for other cytosolic signaling molecules. Tyrosine 132 in human LAT is essential for PLC-γ activation and calcium influx generation. It has been recently reported that a conserved g...

A report sheds new light on the molecular mechanisms responsible for the discrimination of self versus non-self TCR ligands and reveals the crucial role of the kinetics of LAT tyrosine phosphorylation in this.

The adaptor protein linker for activation of T cells (LAT) has an essential role transducing activatory intracellular signals coming from the TCR/CD3 complex. Previous reports have shown that upon T-cell activation, LAT interacts with the tyrosine kinase Lck, leading to the inhibition of its kinase activity. LAT–Lck interaction seemed to depend on...

Stability of WT-linker for activation of T cell (LAT) and LAT-NIL mutant proteins. (A) J.CaM2 cells expressing WT-LAT or the LAT-NIL mutant were treated with cycloheximide (CHX) for indicated times in hours, and LAT and beta-actin protein levels were detected by Western blot. (B) Jurkat cells or the Lck-deficient cell line J.CaM1.6 were treated wit...

Negative impact of linker for activation of T cell (LAT)-NIL expression on activation-induced CD69 expression. Untransduced J.CaM2 cells or transduced with lentiviral vectors coding for WT-LAT or LAT-NIL were stimulated with immobilized anti-CD3 for 18 h at 37°C, and CD69 expression was analyzed by flow cytometry. Left and middle histograms show th...

Expression of WT-linker for activation of T cell (LAT) and LAT-NIL mutant proteins. J.CaM2 cells were lentivirally transduced to express WT-LAT or the LAT-NIL mutant, and the expression of LAT was analyzed 1, 2, 3, and 4 weeks after lentiviral transduction by Western blotting with anti-LAT antibody or anti-6His antibody. Numbers below the blots ind...

Hepatitis C virus core protein is a highly basic viral protein that multimerizes with itself to form the viral capsid. When expressed in CD4⁺ T lymphocytes, it can induce modifications in several essential cellular and biological networks. To shed light on the mechanisms underlying the alterations caused by the viral protein, we have analyzed HCV-c...

Hepatitis C virus (HCV) infection is currently the most important cause of chronic viral hepatitis in the world and one of the most frequent indications for liver transplantation. HCV uses different strategies to evade the innate and adaptive immune response, and this evasion plays a key role in determining viral persistence. Several HCV viral prot...

Non-T cell activation linker is an adaptor protein that is tyrosine phosphorylated upon cross-linking of immune receptors expressed on B lymphocytes, NK cells, macrophages, basophils, or mast cells, allowing the recruitment of cytosolic mediators for downstream signaling pathways. Fas receptor acts mainly as a death receptor, and when cross-linked...

Linker for activation of T cells (LAT) is a transmembrane adaptor protein playing a key role in the development, activation and maintenance of peripheral homeostasis of T cells. In this study we identified a functional isoform of LAT. It originates from an intron 6 retention event generating an in-frame splice variant of LAT mRNA denoted as LATi6....