2021年8月27日 · Interleukin-2–inducible T cell kinase (ITK) is a critical component for the optimal activation of phospholipase-C-gamma-1 (PLC-γ1), the enzyme that cleaves the membrane-embedded phosphatidylinositol bisphosphate into equimolar amounts of two second signaling messengers: inositol triphosphate (IP 3) and diacylglycerol (DAG).

In T cells, the Tec family kinase, ITK, phosphorylates PLCγ1 at tyrosine 783 (Y783) leading to activation of phospholipase function and subsequent production of the second messengers IP 3 and DAG. In this work we demonstrate that PLCγ1 can be primed for ITK mediated phosphorylation on Y783 by a specific region of the adaptor protein, SLP-76.

2022年1月22日 · Here, we review the current molecular level understanding of how the TEC kinases (ITK and BTK) and PLCγ1/2 are autoinhibited prior to activation of cell surface receptors, how TEC kinases are activated to specifically recognize the PLCγ substrate, and how conformational changes induced by phosphorylation trigger PLCγ activation.

2025年1月31日 · An early step in the activation of T cells via the T cell antigen receptor is the phosphorylation and activation of phospholipase C-γ1 (PLC-γ1) by the TEC family tyrosine kinase, interleukin-2 (IL-2) inducible T cell kinase (ITK). PLC-γ1 activation occurs within a multi-protein complex comprised of the enzymes ITK, PLC-γ1, and VAV, and the ...

2005年4月1日 · The TEC-family protein tyrosine kinases ITK, RLK and TEC have been identified as key components of T-cell-receptor signalling that contribute to the regulation of phospholipase C-γ, the ...

Itk (Interleukin-2-inducible T-cell kinase) is a Tec family tyrosine kinase that mediates signaling processes after T cell receptor engagement. Activation of Itk requires recruitment to the membrane via its pleckstrin homology domain, phosphorylation of Itk by the Src kinase, Lck, and binding of Itk to the SLP-76/LAT adapter complex.

IL-2 诱导性 T 细胞激酶 (ITK) 在 T 辅助细胞亚群分化中至关重要，其抑制已被建议用于治疗 T 细胞介导的炎症性疾病。 滤泡辅助性 T (Tfh)、Th17 和调节性 T 细胞 (Treg) 在类风湿性关节炎 (RA) 的发生过程中也发挥着重要作用，而 ITK 在 RA 发生过程中的作用以及效应 T 细胞和调节性 T 细胞之间错综复杂的平衡还不清楚。 在这里，我们发现 RA 患者的 CD4 + T 细胞呈现出升高的 ITK 激活。 ITK 抑制剂可缓解现有的胶原诱导关节炎 (CIA) 并减少抗原特异性抗体的产生。 阻断 ITK …

The nonreceptor tyrosine kinase Itk plays a key role in TCR-initiated signaling that directly and significantly affects the regulation of PLCγ1 and the consequent mobilization of Ca 2+. Itk also participates in the regulation of cytoskeletal reorganization as well as cellular adhesion, which is necessary for a productive T cell response.

Itk functions in TCR signaling via its interactions in the LAT-SLP-76 signaling complex, where it participates in activation of PLC-γ and the downstream generation of DAG and IP 3, as well as regulation of the actin cytoskeleton via interactions with Vav.

2017年8月8日 · Activation of the T cell receptor leads to the formation of a signalosome complex between SLP-76, LAT, PLC-γ1, Itk, and Vav1. Recent studies have revealed the existence of both positive and negative feedback pathways from SLP-76 to the apical kinase in the pathway, Lck.