T cell specific tyrosine kinase

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The T-cell-specific tyrosine kinases belong as enzymes to the tyrosine kinases of the Scr family, Fyn (fibroplast yes-related non receptor kinase) and Lck (lymphocyte kinase). They transfer phosphate groups between proteins , thus transmitting signals and regulating biological processes in the cells . The T cells, more precisely T lymphocytes, are formed in the thymus , they are a group of white blood cells that serve the immune defense .

T-cell-specific tyrosine kinases are catalyzed by tyrosine protein phosphatase C (PTPRC or CD45). These tyrosine kinases are involved in the initiation of the signal transduction of the T cells , which originates from the CD3 complex , since the T cell antigen receptor itself has no intrinsic activity for signal transduction . Ultimately, this cascade leads to the intracellular mobilization of calcium and the activation of important signal cascades within the lymphocytes.

The main component is the tyrosine phosphorylation of the ITAMs sequence motifs ( immunoreceptor tyrosine-based activation motif ) of the y, d and e chains and of the S homodimer of the CD3 complexes. These ITAMs correspond to a conserved section with a YxxLIx6-9YxxLI amino acid sequence and can also be found on typical sequences of the natural killer cell receptors or of the CD79 B cell antigen receptor complex . Since the cell membrane of the T cells is not homogeneous due to its different microdomains with different lipid compositions, the Scr kinases Fyn and Lck do not come into contact with the ITAMs in resting cells. Only after contact with the antigen are the T-cell receptors increasingly found in the cholesterol- and glycosphingolipid-rich rafts, which then leads to an association of Lck with CD4 or CD8, which activates Lck in a previously unexplored way. Fyn is activated through the direct connection of the cytoplasmic sections of CD3S and CD3e.

It is believed that the catalytic activity of both Fyn and LcK is stimulated by autophosphorylation. By activating Lck and Fyn, the tyrosine residues of the ITAMS are phosphated, which creates the binding sites for SH2 domains due to the high electronegativity of the phosphate, which then come from the cytoplasmic tyrosine kinase Zap70 (zeta-associated protein, kD 70) of the Syk kinase family. After this binding process, Lck and Fyn phosphorylate Zap70 tyrosine residues, which activates Zap70.

The activated tyrosine kinase Zap70 can, if a certain threshold value of Zap70 activations within a T cell is exceeded, phosphorylate further tyrosine signal motifs on the transmembrane adapter proteins, which leads to the recruitment of the cytosolic proteins with SH2 domains on the membrane, the cytosolic adapter proteins and enzymes such as Phospholipase Cy, PKC and Ras leads.

Individual evidence

  1. ↑ George A.Holländer: Immunology basis for hospitals and medical practices . Ed .: Elsevier.
  2. ↑ Albrecht Bufe: T-cell receptor, T-cell development, antigen-presenting cells. Retrieved November 16, 2018 .
  3. ↑ a b Christina Schütt, Barbara Bröker: Basic knowledge of immunology . Ed .: Spectrum Academic Publishing House.
  4. ↑ a b Robert J. Salmond: Zamoyska T-cell receptor proximal signalingvia the Src-family kinases, Lck andFyn, influences T-cell activation, . Ed .: Institute for Immunology and Infection Research University of Edinburgh.