DESCRIPTION

The researchers were the first in characterize the DGKalfa (diacilglicerol kinase alpha) as an expressed  enzyme specifically in T cells with an important function as negative modulator in the TCR activation (Sanjuan, 2001 J of Cell Biology). As such, the researchers characterized for the first time the role of this enzyme as a negative regulator of Ras through it`s interaction with DAG (Jones 2002, FASEB J; Sanjuan 2003, J of Inmunol).

DGKalfa is on the cytosol of the lymphocytes and for to do its functions must to translocate to the plasmatic membrane. The researchers described a dependent mechanism of the kinase tyrosine which is essential to modulate the translocation of the enzyme and demonstrate the fosforilation of the endogenous DGKalfa in tyrosine during the lynphocytarie activation. They had identificated the tyrosine residue which result phosphorilated during the activation.

The generation of mutants shows that this residue (tyrosine 355 in the human secuence) is important for the location of the enzyme in the membrane. The generation of an antibody, which recognize specifically the phosphorilated residue, confirm its phosphorilation in primary lymphocytes and in cellular lines and demonstrate that phosphorilated DGKalfa is detected in exclusive form on the membrane. This antibody detects the active portion of the enzyme and provides methods and tools for the diagnostic of immune response illnesses

 INNOVATIVE ASPECTS

The novel regulation mechanism provide methods and tools useful in the treatment and/or diagnostic of lynphoproliferative illness like leukaemia, Hodking and non-Hodking lymphoma, autoimmune illness as well as the improvement of normal and immunodeficiency individuals. These  methods and  therapeutic tools are based on:

(1) Detection proceeding of the phosphorilated level of the DGKalfa`s tyrosine in the residue in question.

(2) Development of screening assays based on the use of this antibody and for identify inhibiting agents or compounds that inhibiting and or active the phosphorilation of the DGKalfa.

(3) Development of therapies to diminish and to promote the phosphorilation of this residue.

(4) Administration of the mutated forms of DGKalfa and/or attenuation of its expression by means of the use of interference RNA.

(5) Use of small molecule that alters the phosphorilation of DGKalfa and another proteins and ligands or block the interactions between phosphorilated proteins and another proteins or ligands that block in manner the phosphorilated DGKalfa function.

(6) Procedure that alters the DGKalfa phosphorilation and modify the protein structure, increase its metabolic processing and/or disable its function

COMPETITIVE ADVANTAGES

It is the only antibody that recognizes a phosphorilated form of diacilglicerol kinase alpha

KEYWORDS

006001 Medicine, human health

006001006 Diagnostics, diagnosis

PATENT

P200701552 applied for 2007-06-05

CONTACT

Eva Gabaldón
email:    eva.gabaldon@orgc.csic.es
phone:   +34 91 585 46 23

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