Disease relevance of Lck

• Identification of Lck-binding elements in tip of herpesvirus saimiri [1].

High impact information on Lck

• Further, we present data indicating that the Lck kinase activates the guanine nucleotide exchange factor and transforming activity of Vav [2].
• However, the functional relevance of hyperosmolarity-induced Fyn and Lck activation remains to be elucidated [3].
• Thus, dephosphorylation of Tyr-505 is not a prerequisite for either phosphorylation of Lck at Tyr-394 or catalytic activation of the kinase [4].
• Here we show that Lck that has been activated by H2O2 is simultaneously phosphorylated at both the carboxyl-terminal tyrosine (Tyr-505) and Tyr-394 [4].
• We have previously shown that exposure of cells to H2O2 strongly activates Lck, a lymphocyte-specific Src family kinase, by inducing phosphorylation on Tyr-394, an absolutely conserved residue within the activation loop of the catalytic domain [4].

Chemical compound and disease context of Lck

• A protein called Tip (tyrosine kinase interacting protein) of herpesvirus saimiri associates with Lck in virus-transformed human T cells and is an in vitro substrate for Lck kinase [1].

Biological context of Lck

• In this paper, we describe the synthesis, structure-activity relationships, and pharmacological characterization of 2-aminopyrimidine carbamates, a new class of compounds with potent and selective inhibition of Lck [5].

Anatomical context of Lck

• Lck, one of eight members of the Src family of tyrosine kinases, is activated after T cell stimulation and is required for T-cell proliferation and interleukin (IL)-2 production [6].
• Inhibition of Lck has been a target to prevent lymphocyte activation and acute rejection [6].
• Lck, a lymphocyte-specific tyrosine protein kinase, is bound to cellular membranes as the result of myristoylation and palmitoylation of its amino terminus [7].
• The activation of T cells in the conjunctiva was assessed by measuring phosphorylation of Lck-associated molecules by Western blot analysis [8].
• The lymphocyte-specific kinase (Lck) is a cytoplasmic tyrosine kinase of the Src family expressed in T cells and NK cells [5].

Associations of Lck with chemical compounds

• Coexpression with Nef did not alter c-Src or Lck tyrosine kinase or transforming activity in this system [9].
• Here, we report the pharmacologic characterization of 1-methyl-1H-indole-2-carboxylic acid (4-{1-[4-(4-acetyl-piperazin-l-yl)-cyclohexyl]-4-amino-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxy-phenyl)-amide (A-770041), an orally bioavailable pyrazolo[3,4-d]pyrimidine with increased selectivity for Lck compared with previously reported compounds [6].
• Novel 2-aminopyrimidine carbamates as potent and orally active inhibitors of Lck: synthesis, SAR, and in vivo antiinflammatory activity [5].

Other interactions of Lck

• We find that Lck, Lyn, and Yes are localized to the postsynaptic density (PSD), the primary structural component of excitatory synapses [10].

Analytical, diagnostic and therapeutic context of Lck

• A-770041, a novel and selective small-molecule inhibitor of Lck, prevents heart allograft rejection [6].
• A small molecule inhibitor of Lck is expected to be useful in the treatment of T cell-mediated autoimmune and inflammatory disorders and/or organ transplant rejection [5].

References