Department of Microbiology and Immunology, McGill University, 3775 University Street, Montréal, QC, Canada.
Dev Comp Immunol. 2010 May;34(5):481-4. doi: 10.1016/j.dci.2009.12.012. Epub 2010 Jan 5.
We previously reported that SHP-1 regulates IRAK-1 activity by binding to an ITIM-like motif found within its kinase domain, which we named kinase tyrosine-based inhibitory motif (KTIM). Herein, we further investigated the presence, number, location, and evolutionary time of emergence of potential KTIMs in many cytosolic kinases, all known to play important roles in the signalling and function of immune cells. We unveil that several kinases contain potential KTIMs, mostly located within their kinase domain and appearing predominantly at the level of early vertebrates becoming highly conserved thereafter. Regarding the KTIMs that were found conserved in both vertebrates and invertebrates, we provide experimental data suggesting that such motifs may have constituted readily available sites that performed new regulatory functions as soon as their binding partners (e.g. SHP-1) appeared in vertebrates. We thus propose KTIMs as novel regulatory motifs in kinases that function through binding to SH2 domain-containing proteins such as SHP-1.
我们之前报道称，SHP-1 通过与其激酶结构域内的 ITIM 样基序结合来调节 IRAK-1 的活性，我们将其命名为激酶酪氨酸基抑制基序（KTIM）。在此，我们进一步研究了许多胞质激酶中潜在 KTIM 的存在、数量、位置和进化时间，这些激酶均已知在免疫细胞的信号转导和功能中发挥重要作用。我们揭示出，几种激酶包含潜在的 KTIM，主要位于其激酶结构域内，并且主要出现在早期脊椎动物中，此后高度保守。对于在脊椎动物和无脊椎动物中都保守的 KTIM，我们提供了实验数据，表明这些基序可能是作为其结合伴侣（例如 SHP-1）一旦在脊椎动物中出现，就能够执行新的调节功能的现成位点。因此，我们提出 KTIM 作为通过与 SH2 结构域包含蛋白（如 SHP-1）结合来发挥作用的激酶中的新型调节基序。
