Affinage

TXK

Tyrosine-protein kinase TXK · UniProt P42681

Length
527 aa
Mass
61.3 kDa
Annotated
2026-04-28
100 papers in source corpus 23 papers cited in narrative 22 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TXK (also called Rlk) is a Tec-family non-receptor tyrosine kinase that couples T cell receptor signaling to both proximal signal transduction and nuclear transcriptional programs governing Th1 cytokine production. Palmitoylated at its N-terminal cysteine string motif, TXK localizes to lipid rafts and is activated by Src-family kinase transphosphorylation at Y420 and autophosphorylation at Y91, functioning independently of PI3K owing to the absence of a pleckstrin homology domain (PMID:9891083, PMID:11353545, PMID:12081135). Downstream of the TCR, TXK phosphorylates SLP-76 and CTLA-4, driving PLCγ1 activation, calcium mobilization, ERK/MAPK signaling, and IL-2 transcription; together with Itk, it is required for normal TCR signal strength, thymocyte selection, NKT cell maturation, and the commitment of CD8+ T cells to a conventional rather than innate-like fate (PMID:10213685, PMID:10660534, PMID:9813138, PMID:16860760, PMID:18292523). Upon T cell activation, TXK translocates to the nucleus where it forms a trimolecular complex with PARP1 and EF-1α that directly binds the IFN-γ promoter at the −53/−39 element and activates Th1-lineage transcription (PMID:10523612, PMID:11859127, PMID:17177976).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1994 Medium

    Identification of TXK as a structurally distinct Tec-family kinase lacking the PH domain established that a non-receptor tyrosine kinase with an atypical domain architecture operates in T cells, raising the question of how it is regulated without canonical lipid-binding modules.

    Evidence cDNA cloning with sequence analysis and Northern blot expression profiling in human tissues

    PMID:7951233

    Open questions at the time
    • No functional data beyond expression pattern
    • Murine ortholog not yet characterized
  2. 1995 Medium

    Preferential expression of Txk in Th1 versus Th2 clones provided the first evidence linking this kinase to a specific T helper lineage, suggesting a selective role in Th1 cytokine regulation.

    Evidence Northern blot comparison across murine Th1 and Th2 T cell clones

    PMID:7829530

    Open questions at the time
    • Correlative expression data only, no loss-of-function test
    • Mechanism of Th1-selective expression unknown
  3. 1999 High

    A series of studies resolved the core activation mechanism: TXK exists as two isoforms generated by alternative translation initiation, with the longer isoform palmitoylated at its cysteine string for cytoplasmic/raft retention and the shorter isoform localizing to the nucleus; Src-family kinases activate TXK downstream of the TCR independently of PI3K, and TXK functions redundantly with Itk to drive PLCγ-dependent calcium, IP3, and MAPK signaling required for T cell proliferation and cytokine production.

    Evidence Palmitoylation assays with cysteine-string mutagenesis, subcellular fractionation, PI3K inhibitor treatment, Btk-deficient DT40 reconstitution, Rlk/Itk double-knockout mouse TCR signaling, transgenic Txk rescue of Itk-null thymic selection

    PMID:10213685 PMID:10224128 PMID:10562318 PMID:9891083

    Open questions at the time
    • Identity of direct substrates beyond PLCγ pathway not yet defined
    • Structural basis for PI3K independence not resolved
  4. 1999 High

    Discovery that TXK translocates to the nucleus upon activation and directly upregulates IFN-γ transcription — a function abolished by NLS deletion — established an unexpected dual role as both a signaling kinase and a transcription factor.

    Evidence IFN-γ promoter–luciferase reporter assay, antisense knockdown, NLS-deletion mutant in Jurkat T cells

    PMID:10523612

    Open questions at the time
    • Precise DNA element not yet mapped
    • Nuclear partners unknown
  5. 1998 Medium

    Identification of CTLA-4 as the first direct substrate of TXK, phosphorylated at the YVKM motif to enable PI3K SH2 domain recruitment, linked TXK kinase activity to co-stimulatory receptor signaling.

    Evidence In vitro kinase assay with PI3K SH2-domain binding assay

    PMID:9813138

    Open questions at the time
    • In vitro only; in vivo phosphorylation of CTLA-4 by TXK not confirmed
    • Functional consequence for T cell inhibitory signaling untested
  6. 2000 High

    Identification of SLP-76 as a TXK substrate at N-terminal YESP/YEPP sites, coupling TXK kinase activity to PLCγ1 phosphorylation, ERK activation, and NFAT/AP-1-driven IL-2 transcription, provided a molecular mechanism for how TXK integrates into the TCR signaling cascade.

    Evidence Co-transfection with kinase-dead mutant controls, SLP-76 phosphorylation-site mutants, luciferase reporter, ERK and PLCγ1 phosphorylation assays

    PMID:10660534

    Open questions at the time
    • Relative contribution of TXK versus Itk to SLP-76 phosphorylation in primary T cells unclear
  7. 2001 High

    Demonstration that TXK associates with lipid rafts via its cysteine string and is activated by Src-family kinase transphosphorylation at Y420, which also regulates protein stability, defined the spatial and regulatory framework for TXK activation at the plasma membrane.

    Evidence Detergent-resistant membrane fractionation, Y420 and cysteine-string mutagenesis, pulse-chase half-life assay, TCR stimulation immunoblotting

    PMID:11353545

    Open questions at the time
    • Identity of specific Src-family kinase(s) responsible not determined
    • Mechanism of phosphorylation-dependent destabilization unknown
  8. 2002 High

    Mapping of the IFN-γ promoter element to −53/−39 bp and identification of Y91 as a TXK autophosphorylation site that positively regulates IFN-γ production refined both the transcriptional target and the activation mechanism.

    Evidence IFN-γ promoter truncation/mutation reporter assays, EMSA, in vitro autophosphorylation assay with Y91A mutagenesis

    PMID:11859127 PMID:12081135

    Open questions at the time
    • Whether Y91 phosphorylation regulates nuclear translocation or DNA binding specifically not resolved
  9. 2003 High

    NMR analysis revealed that the TXK proline-rich/SH3 interaction is intermolecular (dimerization) rather than intramolecular, distinguishing TXK from Itk and implicating dimer formation in TXK regulation.

    Evidence NMR chemical shift, linewidth, and self-diffusion analysis with proline-rich mutagenesis and linker-length variants

    PMID:12798690

    Open questions at the time
    • Functional significance of dimerization for kinase activity or substrate access not tested
    • No crystal structure of full-length TXK
  10. 2006 High

    Genetic studies showed that combined loss of Itk and Rlk redirects CD8+ T cells toward an innate-like (CD44hi, NK1.1+) phenotype rescued by an ERK2 gain-of-function allele, establishing that Tec-kinase-dependent ERK signaling determines the conventional versus innate T cell fate decision.

    Evidence Itk/Rlk double-knockout mice, flow cytometry, ERK2 hypersensitive transgene rescue, in vivo viral infection models

    PMID:16424186 PMID:16860759 PMID:16860760

    Open questions at the time
    • Relative individual contribution of Rlk versus Itk to lineage decision not separated
    • Epigenetic mechanisms downstream of ERK that enforce lineage choice unknown
  11. 2007 High

    Discovery of a trimolecular TXK–PARP1–EF-1α complex that assembles in a kinase-activity-dependent manner and binds the IFN-γ promoter provided the molecular architecture for TXK's dual cytoplasmic kinase/nuclear transcription factor activity.

    Evidence Co-immunoprecipitation, in vitro pulldown, EF-1α phosphorylation assay, EMSA with −53/−39 oligos, kinase-dead mutant, confocal microscopy

    PMID:17177976

    Open questions at the time
    • Stoichiometry and structure of the trimolecular complex unresolved
    • Whether PARP1 enzymatic activity is required not tested
  12. 2008 High

    Loss of Itk/Rlk severely impairs NKT cell maturation and cytokine production, extending Tec kinase function beyond conventional T cells, while transgenic studies showed that selective expression rather than intrinsic functional specificity explains TXK's Th1 association.

    Evidence Itk/Rlk double-KO NKT cell analysis, Txk transgene expressed in Th2 cells rescuing Itk-null Th2 responses

    PMID:18292523 PMID:18941202

    Open questions at the time
    • Whether TXK has any truly unique substrates distinct from Itk remains open
    • NKT cell-intrinsic versus extrinsic contributions not fully separated
  13. 2015 High

    A covalent inhibitor (PRN694) targeting C350 of TXK (and C442 of ITK) validated TXK as a druggable kinase and revealed that combined ITK/TXK inhibition suppresses Th1, Th17 differentiation, and T cell migration, broadening TXK's functional scope to trafficking.

    Evidence Covalent inhibitor design with molecular modeling, in vitro kinase assays, Th polarization, adoptive transfer colitis model, P-selectin binding and chemokine migration assays

    PMID:25593320 PMID:26466958

    Open questions at the time
    • Selective contribution of TXK versus ITK inhibition to the observed phenotypes cannot be separated with a dual inhibitor
    • Structural basis of C350 covalent binding not confirmed by co-crystal structure

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: (1) the full substrate repertoire of TXK distinct from Itk; (2) the structural basis of the trimolecular TXK–PARP1–EF-1α complex; and (3) whether TXK has non-redundant physiological roles separable from Itk in human T cell immunity.
  • No high-resolution structure of full-length TXK or its nuclear complex
  • No human genetic disease linked to TXK loss-of-function
  • TXK-selective inhibitor not yet available to separate its functions from Itk

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0140110 transcription regulator activity 3 GO:0003677 DNA binding 2
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 2 GO:0005886 plasma membrane 1
Pathway
R-HSA-168256 Immune System 5 R-HSA-162582 Signal Transduction 4 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1266738 Developmental Biology 2
Partners
CTLA4EEF1A1ITKPARP1RIBPSLP76
Complex memberships
TXK–PARP1–EF-1α trimolecular complex

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 TXK was identified as a novel cytoplasmic tyrosine kinase expressed primarily in T cells, belonging to the Tec sub-family of Src-type non-receptor tyrosine kinases. Unlike BTK and other Tec family members, TXK lacks a pleckstrin homology domain, Gap 1 homology, and steroid hormone receptor homology in its N-terminal region, and also lacks the C-terminal regulatory tyrosine found in Src kinases. cDNA cloning, sequence analysis, Northern blot expression profiling Human molecular genetics Medium 7951233
1995 Murine Txk (Rlk) is a 62-kDa cytoplasmic tyrosine kinase predominantly expressed in the T cell lineage, with preferential expression in Th1 relative to Th2 T cell clones, suggesting a role in signal transduction pathways that selectively regulate cytokine production in CD4+ T cell subsets. Molecular cloning, expression analysis by Northern blot, T cell subset comparison The Journal of biological chemistry Medium 7829530
1999 Rlk/Txk protein exists as two isoforms arising by alternative initiation of translation from the same cDNA. The larger isoform is palmitoylated at its cysteine string motif and is cytoplasmic, while the shorter internally-initiated isoform lacks the cysteine string and localizes to the nucleus. Mutation of the cysteine string abolishes palmitoylation and causes nuclear relocalization of the larger isoform. Rlk/Txk is phosphorylated by Src family kinases and activated in response to TCR stimulation, but unlike other Btk family members, its activation is independent of phosphatidylinositol 3-kinase activity. Alternative translation initiation analysis, palmitoylation assay, site-directed mutagenesis of cysteine string, subcellular fractionation/localization, in vitro kinase assay, PI3K inhibitor treatment Molecular and cellular biology High 9891083
1999 Txk reconstituted PLCγ2-dependent signaling (calcium mobilization, ERK/MAPK activation) in Btk-deficient DT40 B cells, but unlike other Tec kinases, functioned in a phosphatidylinositol 3-kinase-independent manner and failed to reconstitute apoptosis, consistent with its lack of a pleckstrin homology domain. Reconstitution of Btk-deficient DT40 B cells, calcium flux assay, ERK activation assay, apoptosis assay The Journal of biological chemistry High 10224128
1999 Rlk/Txk and Itk are both required for T cell receptor signaling, specifically for intermediate events including inositol trisphosphate production, calcium mobilization, and MAP kinase activation, establishing Tec kinases as critical regulators required for phospholipase C-gamma activation downstream of the TCR. Combined Rlk/Itk double-knockout mice, TCR signaling assays (IP3, Ca2+ flux, MAPK), proliferation, cytokine production, apoptosis, and in vivo infection model Science (New York, N.Y.) High 10213685
1999 RIBP (Rlk/Itk-binding protein), a T cell-specific adaptor protein, was identified as a binding partner of Rlk/Txk by yeast two-hybrid screen. RIBP also interacts with Itk. RIBP-deficient T cells show impaired proliferation and reduced IL-2 and IFN-γ (but not IL-4) production after TCR stimulation, suggesting RIBP regulates T cell activation downstream of Rlk/Txk and Itk. Yeast two-hybrid screen, RIBP knockout mouse, T cell proliferation and cytokine production assays The Journal of experimental medicine High 10587356
1999 Txk specifically upregulates IFN-γ gene transcription in T cells through nuclear translocation upon activation. A mutant Txk lacking a nuclear localization signal sequence failed to enhance IFN-γ production, demonstrating that nuclear localization of Txk is obligatory for its transcriptional regulatory function. IL-12 enhanced and IL-4 inhibited Txk expression, linking Txk to Th1 differentiation. Txk transfection of Jurkat cells, antisense oligodeoxynucleotide inhibition, luciferase reporter assay (IFN-γ promoter), nuclear localization mutant analysis, cytokine ELISA The Journal of experimental medicine High 10523612
1999 Overexpression of Txk in T cells augments the PLCγ1-mediated calcium signal transduction pathway upon TCR engagement and can partially rescue positive selection defects in itk-/- mice, indicating Txk and Itk perform analogous functions in TCR signaling and thymic selection. Txk transgenic mouse, TCR signaling assays (Ca2+ flux, PLCγ1 activation), thymic selection assay in itk-/- background The Journal of experimental medicine High 10562318
1998 Rlk/Txk phosphorylates the YVKM motif of CTLA-4, the first identified substrate for Rlk, and this phosphorylation creates conditions for binding of the SH2 domains of PI3-kinase to CTLA-4. In vitro kinase assay, biochemical binding assay (PI3-kinase SH2 domain binding) Biochemical and biophysical research communications Medium 9813138
2000 Rlk/Txk phosphorylates SLP-76 at its N-terminal YESP/YEPP sites, leading to PLCγ1 phosphorylation, ERK activation, and synergistic upregulation of TCR-driven IL-2 NFAT/AP-1 transcription. Loss of Rlk kinase activity or the N-terminal SLP-76 phosphorylation sites attenuated this cooperativity. Overexpression/co-transfection, kinase-dead mutant analysis, luciferase reporter assay, ERK and PLCγ1 phosphorylation assays The Journal of biological chemistry High 10660534
2001 Rlk/Txk associates with lipid RAFTs independently of PI3-kinase activity, requiring its cysteine string motif for RAFT association. Rlk is phosphorylated and activated by Src family kinases via Y420 in the activation loop, and this phosphorylation decreases Rlk's half-life. TCR stimulation increases Rlk tyrosine phosphorylation, consistent with Src-mediated activation in T cells. RAFT fractionation (detergent-resistant membrane isolation), PI3K inhibitor treatment, site-directed mutagenesis of Y420 and cysteine string, pulse-chase half-life assay, TCR stimulation and immunoblotting BMC immunology High 11353545
2002 Txk acts as a Th1 cell-specific transcription factor that directly binds to the IFN-γ promoter at a specific element between -53 and -39 bp from the transcription start site. The entire -53/-39 region is necessary for Txk binding and transcriptional activation; contiguous base substitutions throughout this element abolish both binding and Txk-mediated transcriptional upregulation. Luciferase reporter assay with IFN-γ promoter truncations and point mutants, electrophoretic mobility shift assay (EMSA), Txk transfection Journal of immunology (Baltimore, Md. : 1950) High 11859127
2002 Txk autophosphorylates itself in vitro, with Y91 identified as an autophosphorylation site. Mutation of Y91 to alanine reduces Txk-driven IFN-γ production, indicating autophosphorylation at Y91 positively regulates Txk activity. Y420 was previously identified as the Src-family-dependent transphosphorylation site. In vitro kinase autophosphorylation assay, site-directed mutagenesis (Y91A), IFN-γ ELISA after Jurkat transfection Biological & pharmaceutical bulletin Medium 12081135
2003 The proline-rich ligand/SH3 domain interaction in Rlk/Txk occurs in an intermolecular (dimerization) rather than intramolecular fashion, contrasting with Itk where the interaction is exclusively intramolecular. The shorter linker length between the proline-rich ligand and SH3 domain in Rlk compared to Itk is a key structural determinant of this difference in self-association mode. NMR spectroscopy (chemical shift analysis, linewidth, self-diffusion coefficients), site-directed mutagenesis of proline-rich ligand, linker length variants Journal of molecular biology High 12798690
2007 Txk forms a trimolecular complex with poly(ADP-ribose) polymerase 1 (PARP1) and elongation factor 1α (EF-1α) that binds to the IFN-γ gene promoter at the Txk-responsive element (-53/-39). Txk phosphorylates EF-1α, and PARP1 (via its N-terminal DNA-binding domain) bridges the complex. Kinase-inactive Txk mutants cannot form this trimolecular complex. Upon T cell activation, this complex translocates from cytoplasm to nucleus and activates IFN-γ transcription. Co-immunoprecipitation, in vitro binding/pulldown, in vitro kinase assay (EF-1α phosphorylation), EMSA with IFN-γ promoter oligos, kinase-dead mutant analysis, confocal microscopy Clinical and experimental immunology High 17177976
2006 Itk and Rlk/Txk regulate CD8+ T cell development; in their absence, CD8+ T cells adopt an innate-type phenotype (CD44hi, NK1.1+, rapid IFN-γ production), dependent on IL-15. This is associated with increased eomesodermin expression. An ERK2 hypersensitive mutant partially corrects the phenotype, linking Tec kinase-dependent ERK signaling to conventional versus innate CD8+ T cell lineage commitment. Itk/Rlk double-knockout mouse analysis, flow cytometry, cytokine production assays, Erk2 gain-of-function transgene rescue experiment Immunity High 16860759 16860760
2008 Itk and Rlk are required for NKT cell maturation, cytokine production, and peripheral survival. Itk/Rlk double-deficient mice show a 7-fold reduction in invariant NKT cell numbers in the thymus and near-complete absence of cytokine production after in vivo activation. These defects correlate with reduced CD122 (IL-2R/IL-15Rβ) expression and impaired T-bet expression. Itk/Rlk double-knockout mouse analysis, flow cytometry, in vivo NKT cell activation, cytokine ELISA Journal of immunology (Baltimore, Md. : 1950) High 18292523
2015 PRN694, a covalent inhibitor, binds to cysteine 350 of RLK/TXK (and cysteine 442 of ITK) within the ATP-binding site of the kinase domain, blocking kinase activity with extended target residence time. This dual ITK/RLK inhibition prevents TCR-induced T cell proliferation, proinflammatory cytokine release, and Th17 cell activation. Molecular modeling, covalent inhibitor design, in vitro kinase activity assay, cellular TCR signaling assays, T cell proliferation and cytokine assays, in vivo delayed-type hypersensitivity model The Journal of biological chemistry High 25593320
2008 Selective expression rather than intrinsic functional specificity distinguishes Txk and Itk in Th1/Th2 regulation: a Txk transgene expressed at Itk-equivalent levels in Th2 cells rescues Th2 cytokine production and allergic responses in Itk-null mice, without notably enhancing IFN-γ. Txk-null CD4+ T cells produce both Th1 and Th2 cytokines normally. Txk transgene in Itk-/- mice, Th2 disease models (allergic asthma, schistosome egg-induced granuloma), cytokine assays, Txk-null T cell analysis Journal of immunology (Baltimore, Md. : 1950) High 18941202
2006 Loss of Itk and Rlk impairs TCR-dependent signaling in CD8+ T cells, causing defects in PLCγ1, p38, and ERK activation as well as calcium flux and cytokine production in vitro, and expansion and effector cytokine production in vivo after viral infection. These defects could not be rescued by CD4+ T cell help. Itk-/- and Itk/Rlk-/- mouse models, in vitro TCR signaling assays (PLCγ1, p38, ERK phosphorylation, Ca2+ flux), in vivo viral infection model Journal of immunology (Baltimore, Md. : 1950) High 16424186
2015 Inhibition of ITK and RLK with PRN694 impairs Th1 and Th17 differentiation, reduces IFN-γ production by colitogenic CD4+ T cells in vivo, and impairs T cell migration (reduced P-selectin binding and CXCL11/CCL20-induced migration), establishing ITK/RLK as regulators of T cell trafficking as well as differentiation. In vitro Th polarization with covalent inhibitor, T cell adoptive transfer colitis model, P-selectin binding assay, Transwell migration assay Journal of immunology (Baltimore, Md. : 1950) High 26466958
2015 The SH3-binding motif (PxxPxxP) of the PRRSV nucleocapsid protein interacts with TXK via its SH3 domain; disruption of the P53 residue within this motif significantly reduces TXK binding. This identifies TXK SH3 domain engagement as a host interaction exploited by the viral N protein. Yeast two-hybrid, co-immunoprecipitation, site-directed mutagenesis of viral PxxP motif Virus research Medium 25882913

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Requirement for Tec kinases Rlk and Itk in T cell receptor signaling and immunity. Science (New York, N.Y.) 310 10213685
2010 The lysin motif receptor-like kinase (LysM-RLK) CERK1 is a major chitin-binding protein in Arabidopsis thaliana and subject to chitin-induced phosphorylation. The Journal of biological chemistry 302 20610395
2001 The Tec family of cytoplasmic tyrosine kinases: mammalian Btk, Bmx, Itk, Tec, Txk and homologs in other species. BioEssays : news and reviews in molecular, cellular and developmental biology 237 11340625
2011 The RLK/Pelle family of kinases. The Plant journal : for cell and molecular biology 175 21443627
1994 BMX, a novel nonreceptor tyrosine kinase gene of the BTK/ITK/TEC/TXK family located in chromosome Xp22.2. Oncogene 171 7970727
2006 Altered development of CD8+ T cell lineages in mice deficient for the Tec kinases Itk and Rlk. Immunity 159 16860760
2006 The Tec family tyrosine kinases Itk and Rlk regulate the development of conventional CD8+ T cells. Immunity 154 16860759
2017 Origin and diversification of leucine-rich repeat receptor-like protein kinase (LRR-RLK) genes in plants. BMC evolutionary biology 138 28173747
2016 The Arabidopsis Malectin-Like/LRR-RLK IOS1 Is Critical for BAK1-Dependent and BAK1-Independent Pattern-Triggered Immunity. The Plant cell 121 27317676
2011 Cellulose synthesis via the FEI2 RLK/SOS5 pathway and cellulose synthase 5 is required for the structure of seed coat mucilage in Arabidopsis. The Plant journal : for cell and molecular biology 113 21883548
2009 Tec kinases regulate T-lymphocyte development and function: new insights into the roles of Itk and Rlk/Txk. Immunological reviews 112 19290923
2012 The tomato RLK superfamily: phylogeny and functional predictions about the role of the LRRII-RLK subfamily in antiviral defense. BMC plant biology 95 23198823
2008 The Tec kinases Itk and Rlk regulate NKT cell maturation, cytokine production, and survival. Journal of immunology (Baltimore, Md. : 1950) 93 18292523
2016 Evolutionary Dynamics of the Leucine-Rich Repeat Receptor-Like Kinase (LRR-RLK) Subfamily in Angiosperms. Plant physiology 89 26773008
1994 TXK, a novel human tyrosine kinase expressed in T cells shares sequence identity with Tec family kinases and maps to 4p12. Human molecular genetics 84 7951233
1995 Identification of Rlk, a novel protein tyrosine kinase with predominant expression in the T cell lineage. The Journal of biological chemistry 76 7829530
1999 rlk/TXK encodes two forms of a novel cysteine string tyrosine kinase activated by Src family kinases. Molecular and cellular biology 75 9891083
1999 RIBP, a novel Rlk/Txk- and itk-binding adaptor protein that regulates T cell activation. The Journal of experimental medicine 72 10587356
2011 Probing the roles of LRR RLK genes in Arabidopsis thaliana roots using a custom T-DNA insertion set. Plant molecular biology 70 21431781
1999 Txk, a nonreceptor tyrosine kinase of the Tec family, is expressed in T helper type 1 cells and regulates interferon gamma production in human T lymphocytes. The Journal of experimental medicine 70 10523612
2013 The Arabidopsis LRR-RLK, PXC1, is a regulator of secondary wall formation correlated with the TDIF-PXY/TDR-WOX4 signaling pathway. BMC plant biology 66 23815750
2020 Structural evolution drives diversification of the large LRR-RLK gene family. The New phytologist 63 31990988
2014 Molecular dissection of the response of a rice leucine-rich repeat receptor-like kinase (LRR-RLK) gene to abiotic stresses. Journal of plant physiology 63 25173451
2009 The Tec kinases Itk and Rlk regulate conventional versus innate T-cell development. Immunological reviews 63 19290924
2011 Tec family kinases Itk and Rlk / Txk in T lymphocytes: cross-regulation of cytokine production and T-cell fates. The FEBS journal 62 21362139
1998 Challenges in understanding RLK function. Current opinion in plant biology 58 10066619
1999 Reconstitution of Btk signaling by the atypical tec family tyrosine kinases Bmx and Txk. The Journal of biological chemistry 52 10224128
2015 Identification and expression analysis of the LRR-RLK gene family in tomato (Solanum lycopersicum) Heinz 1706. Genome 50 26207619
2007 Txk, a member of the non-receptor tyrosine kinase of the Tec family, forms a complex with poly(ADP-ribose) polymerase 1 and elongation factor 1alpha and regulates interferon-gamma gene transcription in Th1 cells. Clinical and experimental immunology 50 17177976
2002 Txk, a member of nonreceptor tyrosine kinase of Tec family, acts as a Th1 cell-specific transcription factor and regulates IFN-gamma gene transcription. Journal of immunology (Baltimore, Md. : 1950) 49 11859127
1999 A role for the Tec family tyrosine kinase Txk in T cell activation and thymocyte selection. The Journal of experimental medicine 48 10562318
2017 Genome-wide characterization, evolution, and expression analysis of the leucine-rich repeat receptor-like protein kinase (LRR-RLK) gene family in Rosaceae genomes. BMC genomics 44 29017442
2010 Numbers of genes in the NBS and RLK families vary by more than four-fold within a plant species and are regulated by multiple factors. Nucleic acids research 44 20542917
2000 Resting lymphocyte kinase (Rlk/Txk) targets lymphoid adaptor SLP-76 in the cooperative activation of interleukin-2 transcription in T-cells. The Journal of biological chemistry 44 10660534
2021 The RLK protein TaCRK10 activates wheat high-temperature seedling-plant resistance to stripe rust through interacting with TaH2A.1. The Plant journal : for cell and molecular biology 42 34583419
2006 Domain-specific positive selection contributes to the evolution of Arabidopsis leucine-rich repeat receptor-like kinase (LRR RLK) genes. Journal of molecular evolution 42 17031460
2015 Targeting interleukin-2-inducible T-cell kinase (ITK) and resting lymphocyte kinase (RLK) using a novel covalent inhibitor PRN694. The Journal of biological chemistry 41 25593320
2006 Tec kinases Itk and Rlk are required for CD8+ T cell responses to virus infection independent of their role in CD4+ T cell help. Journal of immunology (Baltimore, Md. : 1950) 40 16424186
2006 Skewed Th1 responses caused by excessive expression of Txk, a member of the Tec family of tyrosine kinases, in patients with Behcet's disease. Clinical medicine & research 38 16809408
1987 Additional member of the protein-tyrosine kinase family: the src- and lck-related protooncogene c-tkl. Proceedings of the National Academy of Sciences of the United States of America 38 3321053
2020 The LRR-RLK Protein HSL3 Regulates Stomatal Closure and the Drought Stress Response by Modulating Hydrogen Peroxide Homeostasis. Frontiers in plant science 37 33329622
2005 Excessive expression of Txk, a member of the Tec family of tyrosine kinases, contributes to excessive Th1 cytokine production by T lymphocytes in patients with Behcet's disease. Clinical and experimental immunology 37 15654836
1995 Murine txk: a protein tyrosine kinase gene regulated by T cell activation. Oncogene 37 7542761
2018 A malectin-like/leucine-rich repeat receptor protein kinase gene, RLK-V, regulates powdery mildew resistance in wheat. Molecular plant pathology 36 30030900
2018 Identification and Characterization of LRR-RLK Family Genes in Potato Reveal Their Involvement in Peptide Signaling of Cell Fate Decisions and Biotic/Abiotic Stress Responses. Cells 36 30150583
2008 Selective expression rather than specific function of Txk and Itk regulate Th1 and Th2 responses. Journal of immunology (Baltimore, Md. : 1950) 35 18941202
2001 Requirements for activation and RAFT localization of the T-lymphocyte kinase Rlk/Txk. BMC immunology 34 11353545
2023 Phylogeny of the plant receptor-like kinase (RLK) gene family and expression analysis of wheat RLK genes in response to biotic and abiotic stresses. BMC genomics 32 37127571
2016 LRR-RLK family from two Citrus species: genome-wide identification and evolutionary aspects. BMC genomics 31 27515968
2015 A Small Molecule Inhibitor of ITK and RLK Impairs Th1 Differentiation and Prevents Colitis Disease Progression. Journal of immunology (Baltimore, Md. : 1950) 29 26466958
2015 Somatic embryogenesis receptor-like kinase 5 in the ecotype Landsberg erecta of Arabidopsis is a functional RD LRR-RLK in regulating brassinosteroid signaling and cell death control. Frontiers in plant science 29 26528315
2011 Soybean cyst nematode resistance in soybean is independent of the Rhg4 locus LRR-RLK gene. Functional & integrative genomics 29 21541782
2020 RLP/K enrichment sequencing; a novel method to identify receptor-like protein (RLP) and receptor-like kinase (RLK) genes. The New phytologist 28 32285454
2008 Phylogeny of Tec family kinases identification of a premetazoan origin of Btk, Bmx, Itk, Tec, Txk, and the Btk regulator SH3BP5. Advances in genetics 27 19161832
2003 Determinants of intra versus intermolecular self-association within the regulatory domains of Rlk and Itk. Journal of molecular biology 27 12798690
1998 Resting lymphocyte kinase (Rlk/Txk) phosphorylates the YVKM motif and regulates PI 3-kinase binding to T-cell antigen CTLA-4. Biochemical and biophysical research communications 27 9813138
2021 A novel LRR-RLK (CTLK) confers cold tolerance through regulation on the C-repeat-binding factor pathway, antioxidants, and proline accumulation. The Plant journal : for cell and molecular biology 26 34626033
2017 A deletion affecting an LRR-RLK gene co-segregates with the fruit flat shape trait in peach. Scientific reports 25 28751691
2020 Computational identification of receptor-like kinases "RLK" and receptor-like proteins "RLP" in legumes. BMC genomics 23 32620079
1992 tkl is the avian homolog of the mammalian lck tyrosine protein kinase gene. Molecular and cellular biology 22 1545804
2018 Genome-Wide Analysis of LRR-RLK Gene Family in Four Gossypium Species and Expression Analysis during Cotton Development and Stress Responses. Genes 21 30501109
2023 Genome-wide identification of the LRR-RLK gene family in peanut and functional characterization of AhLRR-RLK265 in salt and drought stresses. International journal of biological macromolecules 20 37926304
2021 Genome-Wide Identification of LRR-RLK Family in Saccharum and Expression Analysis in Response to Biotic and Abiotic Stress. Current issues in molecular biology 20 34698114
2019 Investigation of evolutionary and expressional relationships in the function of the leucine-rich repeat receptor-like protein kinase gene family (LRR-RLK) in the radish (Raphanus sativus L.). Scientific reports 19 31061443
2018 Identification and comprehensive analysis of the characteristics and roles of leucine-rich repeat receptor-like protein kinase (LRR-RLK) genes in Sedum alfredii Hance responding to cadmium stress. Ecotoxicology and environmental safety 19 30312890
2016 Duplication and Divergence of Leucine-Rich Repeat Receptor-Like Protein Kinase (LRR-RLK) Genes in Basal Angiosperm Amborella trichopoda. Frontiers in plant science 19 28066499
1996 Human Txk: genomic organization, structure and contiguous physical linkage with the Tec gene. Oncogene 18 8632917
2021 Analyses of Lysin-motif Receptor-like Kinase (LysM-RLK) Gene Family in Allotetraploid Brassica napus L. and Its Progenitor Species: An In Silico Study. Cells 16 35011598
2010 COE1, an LRR-RLK responsible for commissural vein pattern formation in rice. The Plant journal : for cell and molecular biology 16 20487383
2016 Alternative splicing of the receptor-like kinase Nt-Sd-RLK in tobacco cells responding to lipopolysaccharides: suggestive of a role in pathogen surveillance and perception? FEBS letters 15 27657914
2007 Role of Txk, a member of the Tec family of tyrosine kinases, in immune-inflammatory diseases. International reviews of immunology 15 18027204
2022 Spatial range, temporal span, and promiscuity of CLE-RLK signaling. Frontiers in plant science 14 36092449
2020 Analysis of QTL DM4.1 for Downy Mildew Resistance in Cucumber Reveals Multiple subQTL: A Novel RLK as Candidate Gene for the Most Important subQTL. Frontiers in plant science 14 33193500
2019 New sources of Sym2 allele in the pea (Pisum sativum L.) carry the unique variant of candidate LysM-RLK gene LykX. PeerJ 14 31768303
2018 Evolution, functional differentiation, and co-expression of the RLK gene family revealed in Jilin ginseng, Panax ginseng C.A. Meyer. Molecular genetics and genomics : MGG 14 29468273
2017 ITK and RLK Inhibitor PRN694 Improves Skin Disease in Two Mouse Models of Psoriasis. The Journal of investigative dermatology 14 29129599
1984 Fate and structure of DNA microinjected into mouse TK-L cells. Experimental cell research 14 6734747
2024 An LRR-RLK protein modulates drought- and salt-stress responses in maize. Journal of genetics and genomics = Yi chuan xue bao 13 39547547
2020 Genome-Wide Characterization, Evolution, and Expression Analysis of the Leucine-Rich Repeat Receptor-Like Protein Kinase (LRR-RLK) Gene Family in Medicago truncatula. Life (Basel, Switzerland) 13 32899802
2019 Genome-wide in silico identification of LysM-RLK genes in potato (Solanum tuberosum L.). Molecular biology reports 13 31317454
2019 Aphid resistance in Capsicum maps to a locus containing LRR-RLK gene analogues. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 13 31595336
2018 Lack of a Cytoplasmic RLK, Required for ROS Homeostasis, Induces Strong Resistance to Bacterial Leaf Blight in Rice. Frontiers in plant science 13 29868050
2015 An SH3 binding motif within the nucleocapsid protein of porcine reproductive and respiratory syndrome virus interacts with the host cellular signaling proteins STAMI, TXK, Fyn, Hck, and cortactin. Virus research 13 25882913
2001 Biochemical and genetic analyses of the Tec kinases Itk and Rlk/Txk. Biochemical Society transactions 12 11709089
2023 Evolution of Lipochitooligosaccharide Binding to a LysM-RLK for Nodulation in Medicago truncatula. Plant & cell physiology 11 37098213
2021 Orthology and synteny analysis of receptor-like kinases "RLK" and receptor-like proteins "RLP" in legumes. BMC genomics 11 33568053
2020 SGT1 is not required for plant LRR-RLK-mediated immunity. Molecular plant pathology 11 33174685
2004 Th1-dominant shift of T cell cytokine production, and subsequent reduction of serum immunoglobulin E response by administration in vivo of plasmid expressing Txk/Rlk, a member of Tec family tyrosine kinases, in a mouse model. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 11 15196287
2002 Evidence of autophosphorylation in Txk: Y91 is an autophosphorylation site. Biological & pharmaceutical bulletin 11 12081135
2018 The overexpression of RXam1, a cassava gene coding for an RLK, confers disease resistance to Xanthomonas axonopodis pv. manihotis. Planta 10 29453662
2017 Root cone angle is enlarged in docs1 LRR-RLK mutants in rice. Rice (New York, N.Y.) 10 29247303
2007 The related adaptors, adaptor in lymphocytes of unknown function X and Rlk/Itk-binding protein, have nonredundant functions in lymphocytes. Journal of immunology (Baltimore, Md. : 1950) 10 17641043
2023 Genome-wide analysis and characterization of the LRR-RLK gene family provides insights into anthracnose resistance in common bean. Scientific reports 9 37596307
2021 Effects of Txk‑mediated activation of NF‑κB signaling pathway on neurological deficit and oxidative stress after ischemia‑reperfusion in rats. Molecular medicine reports 9 34036382
2014 Kinase domain-targeted isolation of defense-related receptor-like kinases (RLK/Pelle) in Platanus×acerifolia: phylogenetic and structural analysis. BMC research notes 9 25486898
2024 Overexpression of rice lectin receptor-like kinase, OsLec-RLK, confers salinity stress tolerance and increases seed yield in pigeon pea (Cajanus cajan (L.) Millsp.). Plant cell reports 8 39251423
2023 Differential expansion and retention patterns of LRR-RLK genes across plant evolution. Plant direct 8 38145254
2017 Genome scanning for identification and mapping of receptor-like kinase (RLK) gene superfamily in Solanum tuberosum. Physiology and molecular biology of plants : an international journal of functional plant biology 8 29158626
2023 Recognition of Pep-13/25 MAMPs of Phytophthora localizes to an RLK locus in Solanum microdontum. Frontiers in plant science 7 36714772
2022 Identification of leucine-rich repeat receptor-like protein kinase (LRR-RLK) genes in paper mulberry and their potential roles in response to cold stress. Computational biology and chemistry 7 35033836