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These data indicate that PRN694 is a highly selective and potent covalent inhibitor of ITK (show ITK Proteins) and RLK, and its extended target residence time enables durable attenuation of effector cells in vitro and in vivo.
fuctions as a Th1 (show TH1L Proteins) cell-specific transcription factor and regulates IFN-gamma (show IFNG Proteins) gene transcription
Th1 (show TH1L Proteins) cells expressing Txk and Th1 (show TH1L Proteins)-associated cytokines may play a critical role in the development of skin and intestinal lesions in patients with Behcet's disease.
Itk (show ITK Proteins) 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 (show TH1L Proteins) responses.
Taken together, these data indicate that ITK (show ITK Proteins) plus RLK inhibition may have therapeutic potential in Th1 (show HAND1 Proteins)-mediated inflammatory diseases.
TXK plays an overlapping role with ITK (show ITK Proteins) in iNKT cell development and function. ITK (show ITK Proteins) also has a unique function in the survival of iNKT cells, likely via a p53 (show TP53 Proteins)-dependent pathway.
The protein data combined with the association constants for binding of each proline-rich peptide to the corresponding SH3 domain provide an explanation for the opposing modes of self-association within the otherwise closely related Rlk and Itk (show ITK Proteins) proteins
Tec kinases play key roles in regulating TCR-mediated polarization of integrins and signaling molecules to the site of TCR stimulation as well as the up-regulation of integrin adhesion.
A role for Rlk kinase is demonstrated in CD8 (show CD8A Proteins)+ T cell signaling and function both in vitro and in vivo.
indicate a critical role for Itk (show ITK Proteins) and Rlk in conventional CD8 (show CD8A Proteins)(+) T cell development in the thymus
Tec kinases differentially regulate development of conventional versus nonconventional lymphocytes
Tec (show NR4A3 Proteins) kinases Rlk and Itk (show ITK Proteins) together provide important signals for terminal maturation, efficient cytokine production, and peripheral survival of natural killer T (NKT (show CTSL1 Proteins)) cells.
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