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These data indicate that PRN694 is a highly selective and potent covalent inhibitor of ITK and RLK, and its extended target residence time enables durable attenuation of effector cells in vitro and in vivo.
fuctions as a Th1 cell-specific transcription factor and regulates IFN-gamma gene transcription
Th1 cells expressing Txk and Th1-associated cytokines may play a critical role in the development of skin and intestinal lesions in patients with Behcet's disease.
Itk and Txk exert their effects on T helper (Th) cell differentiation and function at the level of expression; transgenic Txk is not a specific regulator of Th1 responses.
Non-receptor tyrosine kinase that plays a redundant role with ITK in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T- cells and nonconventional NKT-cells. When antigen presenting cells (APC) activate T-cell receptor (TCR), a series of phosphorylation lead to the recruitment of TXK to the cell membrane, where it is phosphorylated at Tyr-420. Phosphorylation leads to TXK full activation. Contributes also to signaling from many receptors and participates in multiple downstream pathways, including regulation of the actin cytoskekleton. Like ITK, can phosphorylate PLCG1, leading to its localization in lipid rafts and activation, followed by subsequent cleavage of its substrates. In turn, the endoplasmic reticulum releases calcium in the cytoplasm and the nuclear activator of activated T-cells (NFAT) translocates into the nucleus to perform its transcriptional duty. With PARP1 and EEF1A1, TXK forms a complex that acts as a T-helper 1 (Th1) cell- specific transcription factor and binds the promoter of IFNG to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production. Phosphorylates both PARP1 and EEF1A1. Phosphorylates also key sites in LCP2 leading to the up-regulation of Th1 preferred cytokine IL-2. Phosphorylates 'Tyr- 201' of CTLA4 which leads to the association of PI-3 kinase with the CTLA4 receptor.
PTK4 protein tyrosine kinase 4
, protein-tyrosine kinase 4
, resting lymphocyte kinase
, tyrosine kinase
, tyrosine-protein kinase TXK
, TXK tyrosine kinase
, tyrosine-protein kinase TXK-like
, LOW QUALITY PROTEIN: tyrosine-protein kinase TXK