Affinage

TXK

Tyrosine-protein kinase TXK · UniProt P42681

Length
527 aa
Mass
61.3 kDa
Annotated
2026-06-10
100 papers in source corpus 22 papers cited in narrative 21 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TXK (Rlk) is a Tec-family non-receptor tyrosine kinase expressed primarily in T cells that, acting redundantly with Itk, couples T cell receptor (TCR) engagement to phospholipase C-gamma1 activation, calcium mobilization, and MAP kinase signaling, positioned between early TCR-proximal events (ZAP-70, Src kinases) and PLC-gamma (PMID:10213685, PMID:16424186). Structurally distinct from other Tec kinases, TXK lacks the PH, Gap1-homology, and steroid-hormone-receptor-homology regions while retaining SH3, SH2, and catalytic domains (PMID:7951233); instead of a PH domain it carries a unique N-terminal palmitoylated cysteine-string motif that targets the kinase to lipid rafts independently of PI3-kinase, with mutation of the cysteine string abolishing palmitoylation and redirecting the protein to the nucleus (PMID:9891083, PMID:11353545). Activation requires Src-family kinase phosphorylation of the activation-loop tyrosine Y420 and is reinforced by autophosphorylation at Y91 (PMID:11353545, PMID:12081135). Active TXK phosphorylates the adaptor SLP-76 in a pathway parallel to ZAP-70 to drive PLC-gamma1 phosphorylation, ERK activation, and TCR-driven transcription (PMID:10660534), and also phosphorylates CTLA-4 to create a PI3-kinase SH2-binding site (PMID:9813138). Upon TCR activation TXK translocates to the nucleus, where it acts as a transcription factor binding a discrete IFN-gamma promoter element (-53/-39) as part of a trimolecular complex with PARP1 and EF-1alpha to drive IFN-gamma transcription (PMID:10523612, PMID:11859127, PMID:17177976). At the developmental level, combined Itk/Rlk loss is required for conventional CD8+ T cell, NKT cell, and Th2 responses, and their association with Th1/IFN-gamma output reflects preferential Th1 expression rather than intrinsic Th1 signaling specificity (PMID:16860759, PMID:16860760, PMID:18941202).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1994 Medium

    Established TXK as a distinct Tec-family cytoplasmic tyrosine kinase, defining the structural feature — absence of a PH domain — that would prove central to its unique regulation.

    Evidence cDNA cloning, Northern expression analysis, and chromosomal mapping

    PMID:7951233

    Open questions at the time
    • No functional role assigned at cloning
    • Mechanism of membrane targeting without a PH domain unresolved at this stage
  2. 1999 High

    Placed TXK/Rlk and Itk genetically between proximal TCR signaling and PLC-gamma, answering where Tec kinases act in the TCR cascade.

    Evidence rlk-/-itk-/- double-knockout mice with IP3, calcium, and MAPK readouts in vitro and in vivo

    PMID:10213685

    Open questions at the time
    • Direct substrate linking Tec kinases to PLC-gamma not yet identified
    • Individual contribution of TXK versus Itk not resolved
  3. 1999 High

    Explained how TXK localizes without a PH domain and revealed a dual cytoplasmic/nuclear distribution governed by palmitoylation, predicting a nuclear function.

    Evidence Translation-initiation isoform analysis, palmitoylation assay, cysteine-string mutagenesis, fractionation, and Src co-expression kinase assays

    PMID:9891083

    Open questions at the time
    • Nuclear function not yet defined
    • PI3-kinase-independence shown but downstream effectors of activation not mapped
  4. 1999 High

    Demonstrated that the missing PH domain accounts for a functional difference among Tec kinases — TXK reconstitutes calcium/ERK signaling but not apoptosis.

    Evidence Reconstitution of Btk-deficient DT40 B cells with calcium, ERK, and apoptosis readouts

    PMID:10224128

    Open questions at the time
    • Heterologous B-cell system may not fully reflect T-cell context
    • Mechanism of PH-dependent apoptotic function not defined
  5. 1999 High

    Showed functional overlap and dose-sensitivity with Itk in thymic selection, establishing TXK as a modulator of PLC-gamma1 signaling in development.

    Evidence Txk transgenic mice, calcium/PLC-gamma1 assays, and thymocyte selection in itk-/- background

    PMID:10562318

    Open questions at the time
    • Mechanism of inhibitory effect upon overexpression unclear
    • Endogenous TXK contribution to selection not isolated
  6. 1999 Medium

    Identified RIBP as a direct TXK/Itk-binding adaptor regulating TCR-induced proliferation and Th1 cytokine output.

    Evidence Yeast two-hybrid screen and RIBP-knockout mouse proliferation/cytokine assays

    PMID:10587356

    Open questions at the time
    • Direct interaction in primary T cells not confirmed in abstract
    • How RIBP modulates TXK kinase activity unknown
  7. 1999 High

    Linked TXK to selective IFN-gamma production and established that nuclear translocation is required for this transcriptional function.

    Evidence Jurkat transfection, IFN-gamma reporter assay, antisense knockdown, and NLS-mutant localization analysis

    PMID:10523612

    Open questions at the time
    • Direct DNA target and nuclear partners not yet identified
    • Whether kinase activity is required for nuclear function untested here
  8. 1998 Medium

    Identified CTLA-4 as the first TXK substrate, coupling TXK kinase activity to inhibitory receptor signaling via PI3-kinase recruitment.

    Evidence In vitro kinase assay and PI3-kinase SH2 domain binding assay

    PMID:9813138

    Open questions at the time
    • No mutagenesis confirmation of the phosphosite in abstract
    • Physiological relevance in T cells not established
  9. 2000 Medium

    Defined SLP-76 as a TXK substrate, placing TXK in a ZAP-70-parallel pathway that drives PLC-gamma1/ERK and TCR transcriptional output.

    Evidence Co-transfection, IL-2 NFAT/AP-1 reporter, and phosphosite-mutant SLP-76 phosphorylation assays

    PMID:10660534

    Open questions at the time
    • In-cell overexpression context only
    • Endogenous stoichiometry of TXK versus ZAP-70 on SLP-76 unknown
  10. 2001 High

    Resolved the activation logic: raft targeting depends on the cysteine-string motif while catalytic activation depends on Src-mediated Y420 phosphorylation, decoupling localization from kinase activation.

    Evidence Detergent-resistant membrane fractionation, Y420 mutagenesis, PI3-kinase inhibition, and protein half-life measurements

    PMID:11353545

    Open questions at the time
    • Identity of the relevant Src-family kinase in vivo not pinned down
    • Link between Y420 phosphorylation and decreased stability mechanistically unexplained
  11. 2002 Medium

    Mapped TXK's direct DNA-binding element on the IFN-gamma promoter (-53/-39), establishing TXK as a sequence-specific transcriptional regulator.

    Evidence IFN-gamma promoter deletion/mutation reporter assays and DNA-binding (EMSA-type) assays

    PMID:11859127

    Open questions at the time
    • Whether TXK binds DNA directly or via partners not resolved here
    • Co-factors at the element not yet identified
  12. 2002 Medium

    Established Y91 autophosphorylation as a positive regulator of TXK function, linking catalytic activity to IFN-gamma output.

    Evidence In vitro autophosphorylation assay, ATP-site and Y91A mutants, and IFN-gamma ELISA in Jurkat cells

    PMID:12081135

    Open questions at the time
    • Functional readout (cytokine) is indirect
    • Order of Y91 autophosphorylation relative to Y420 not defined
  13. 2003 High

    Revealed a structural distinction from Itk: TXK's short proline-rich-to-SH3 linker enforces intermolecular (dimerizing) SH3 engagement rather than autoinhibitory intramolecular binding.

    Evidence NMR chemical-shift, linewidth, and self-diffusion analysis with proline and linker-length mutants

    PMID:12798690

    Open questions at the time
    • Functional consequence of intermolecular dimerization for signaling untested
    • In-cell relevance of the dimerized state unknown
  14. 2006 High

    Demonstrated that Itk/Rlk are required for conventional CD8+ T cell development and TCR signaling, with their loss diverting cells to an innate IFN-gamma-producing program.

    Evidence Itk-/- and Rlk-/-Itk-/- mice with flow cytometry, signaling assays, viral infection, and eomesodermin analysis

    PMID:16424186 PMID:16860759 PMID:16860760

    Open questions at the time
    • TXK-specific contribution separate from Itk not isolated
    • Mechanism by which Tec kinases suppress the innate program unresolved
  15. 2007 High

    Defined the nuclear transcriptional machinery: TXK forms a PARP1/EF-1alpha trimolecular complex on the IFN-gamma promoter, requiring TXK kinase activity and phosphorylating EF-1alpha.

    Evidence Co-IP, in vitro kinase assay, DNA-binding assay, confocal imaging, PARP1 inhibitor, and kinase-dead/domain-deletion mutants

    PMID:17177976

    Open questions at the time
    • Whether TXK or PARP1 provides DNA-binding specificity not fully resolved
    • All evidence from one lab
  16. 2008 Medium

    Extended the Itk/Rlk requirement to NKT cell terminal maturation and survival, broadening the developmental scope of TXK.

    Evidence Itk-/- and Itk/Rlk-/- mice with flow cytometry, in vivo cytokine, and cell-death assays

    PMID:18292523

    Open questions at the time
    • Cell-intrinsic TXK requirement not formally separated from Itk
    • Single lab
  17. 2008 High

    Resolved the Th1-association question: TXK and Itk share signaling specificity, and TXK's link to IFN-gamma reflects its preferential Th1 expression, not an intrinsic Th1-specific function.

    Evidence Txk-null mice and Itk-/- mice bearing a Txk transgene tested in two Th2 disease models with cytokine ELISA

    PMID:18941202

    Open questions at the time
    • Reconciliation with TXK's direct IFN-gamma transcriptional role not fully integrated
    • Determinants of preferential Th1 expression unknown
  18. 2015 Medium

    Provided a pharmacological tool: the covalent inhibitor PRN694 targets TXK Cys350 (and Itk Cys442) at the ATP site, blocking TCR-driven proliferation, cytokine production, and Th17 activation.

    Evidence Molecular modeling, covalent kinase assays, TEC-family selectivity profiling, and cellular functional assays

    PMID:25593320

    Open questions at the time
    • TXK-selective inhibition not achieved (dual TXK/Itk)
    • In vivo efficacy not addressed in this finding
  19. 2015 Low

    Identified a viral interaction in which the TXK SH3 domain binds the PRRSV nucleocapsid PxxP motif.

    Evidence Co-IP, PxxP mutagenesis, and steric-hindrance fluorescent assay

    PMID:25882913

    Open questions at the time
    • Single Co-IP without reciprocal validation; functional consequence for TXK not established
    • Relevance to host T cell biology unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TXK reconciles its cytoplasmic raft-associated kinase signaling with its sequence-specific nuclear transcriptional role, and what distinguishes its function from Itk beyond expression pattern, remains unresolved.
  • No structure of the TXK-PARP1-EF-1alpha-DNA complex
  • TXK-specific (Itk-independent) signaling and developmental functions not isolated
  • Regulation of cytoplasm-to-nucleus translocation not mechanistically defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0016740 transferase activity 3 GO:0140110 transcription regulator activity 3 GO:0003677 DNA binding 2
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 3 GO:0005886 plasma membrane 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 4 R-HSA-74160 Gene expression (Transcription) 3
Partners
CSK/SFKCTLA-4EEF1A1ITKPARP1RIBPSLP-76
Complex memberships
TXK-PARP1-EF-1alpha IFN-gamma promoter complex

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Combined deletion of Rlk (TXK) and Itk in mice causes defects in TCR-induced inositol trisphosphate production, calcium mobilization, and MAP kinase activation, establishing that Tec kinases are required for phospholipase C-gamma activation downstream of the TCR. Molecular events immediately upstream (ZAP-70, Src kinase activation) were intact, placing Rlk/Txk between early TCR signaling and PLC-gamma. Genetic knockout (rlk-/-itk-/- double-mutant mice) with in vitro TCR signaling assays (IP3 production, calcium flux, MAPK activation) and in vivo immune challenge Science High 10213685
1999 Rlk/Txk protein exists as two isoforms arising by alternative translational initiation from the same cDNA. The larger isoform is palmitoylated via its unique N-terminal cysteine-string motif, which directs cytoplasmic localization; mutation of the cysteine string abolishes palmitoylation and causes nuclear translocation. The shorter isoform, lacking the cysteine string, localizes to the nucleus. Rlk is phosphorylated and activated by Src family kinases independently of PI3-kinase activity (consistent with its lack of a PH domain), and its localization changes upon TCR activation. Isoform characterization by translation initiation mutagenesis; palmitoylation assay; subcellular fractionation/immunofluorescence; kinase activation assay with Src family kinase co-expression; PI3-kinase inhibitor studies Molecular and cellular biology High 9891083
1999 Txk reconstituted PLCgamma2-dependent calcium mobilization and ERK/MAPK activation in Btk-deficient DT40 B cells, but unlike other Tec kinases, functioned in a PI3-kinase-independent manner and failed to reconstitute apoptosis. This demonstrates that the PH domain (absent in Txk) is required for the apoptotic function of Tec kinases. Reconstitution of Btk-deficient DT40 cells with Txk expression; calcium flux assay; ERK activation assay; apoptosis assay The Journal of biological chemistry High 10224128
1999 Txk specifically augments the PLC-gamma1-mediated calcium signaling pathway upon TCR engagement when overexpressed in T cells. Transgenic Txk partially rescued defects in positive selection and signaling in itk-/- mice, indicating functional overlap with Itk. Conversely, Txk overexpression in wild-type mice inhibited positive selection of TCR-transgenic thymocytes. Txk transgenic mouse model; TCR signaling assays (calcium flux, PLC-gamma1 activation); thymocyte selection analysis in itk-/- background The Journal of experimental medicine High 10562318
1999 RIBP (Rlk/Itk-binding protein), a T cell-specific adaptor, was identified as a direct binding partner of Rlk/Txk by yeast two-hybrid screening. RIBP also binds Itk. RIBP-deficient T cells show impaired TCR-induced proliferation and reduced IL-2 and IFN-gamma (but not IL-4) production, indicating RIBP regulates TCR signaling downstream of Rlk/Txk. Yeast two-hybrid screen; RIBP knockout mice; T cell proliferation and cytokine production assays The Journal of experimental medicine Medium 10587356
1999 Txk is expressed preferentially in Th1/Th0 cells, and transfection of Txk into Jurkat T cells increases IFN-gamma mRNA and protein production specifically (IL-2 and IL-4 unaffected). Txk translocates from cytoplasm to nucleus upon activation. A Txk mutant lacking a nuclear localization signal failed to enhance IFN-gamma production, establishing that nuclear translocation is required for Txk-driven IFN-gamma gene transcription. IL-12 upregulates Txk expression; IL-4 suppresses it. Txk transfection in Jurkat cells; IFN-gamma promoter/luciferase reporter assay; antisense oligonucleotide inhibition; subcellular localization by immunofluorescence; nuclear localization signal mutant The Journal of experimental medicine High 10523612
2000 Rlk/Txk phosphorylates the adaptor SLP-76 at its N-terminal YESP/YEPP sites, leading to PLCgamma1 phosphorylation, ERK activation, and synergistic upregulation of TCR-driven IL-2 NFAT/AP-1 transcription. Loss of these SLP-76 phosphorylation sites or Rlk kinase activity attenuated cooperativity, placing Rlk in a pathway parallel to ZAP-70 for SLP-76 phosphorylation. Co-transfection; IL-2 NFAT/AP-1 luciferase reporter; phosphorylation assays with mutant SLP-76 constructs; PLCgamma1 and ERK activation assays The Journal of biological chemistry Medium 10660534
1998 Rlk/Txk directly phosphorylates CTLA-4 at the YVKM motif in vitro, and this phosphorylation creates conditions for PI3-kinase SH2 domain binding to CTLA-4, identifying CTLA-4 as the first known substrate of Rlk. In vitro kinase assay; PI3-kinase SH2 domain binding assay Biochemical and biophysical research communications Medium 9813138
2001 Rlk/Txk is associated with lipid RAFTs independently of PI3-kinase activity, and this RAFT association requires the cysteine-string motif. Src family kinase-dependent phosphorylation of activation loop tyrosine Y420 is required for Rlk kinase activation and decreased protein stability, but not for RAFT association. TCR stimulation induces increased Rlk tyrosine phosphorylation, dependent on Y420. Detergent-resistant membrane fractionation (RAFT isolation); site-directed mutagenesis of Y420; PI3-kinase inhibitor treatment; Src kinase co-expression and phosphorylation assays; half-life measurements BMC immunology High 11353545
2002 Txk acts as a Th1 cell-specific transcription factor by directly binding to an IFN-gamma promoter element between -53 and -39 bp from the transcription start site. This site is distinct from previously characterized binding sites, and contiguous base substitutions throughout the -53/-39 region abolished both binding and promoter responsiveness to Txk. IFN-gamma promoter deletion/mutation luciferase reporter assays; DNA-binding assays (EMSA-type) with Txk and promoter oligonucleotides Journal of immunology Medium 11859127
2002 Txk autophosphorylates in vitro; Y91 is an autophosphorylation site. Disruption of the ATP-binding site (kinase-dead mutant) abolished IFN-gamma production in transfected Jurkat cells, and Y91A mutation reduced IFN-gamma production, establishing that autophosphorylation at Y91 positively regulates Txk function. In vitro kinase assay; site-directed mutagenesis (ATP-binding site, Y91A); IFN-gamma ELISA from transfected Jurkat cells Biological & pharmaceutical bulletin Medium 12081135
2003 The proline-rich ligand/SH3 domain interaction in Rlk/Txk occurs exclusively in an intermolecular (dimerization) fashion, in contrast to Itk where it is intramolecular. This difference is determined by the shorter linker length between the proline-rich ligand and SH3 domain in Rlk. Lengthening the Rlk linker shifts it toward intramolecular binding, and shortening the Itk linker reduces intramolecular binding. NMR spectroscopy (concentration-dependent chemical shift analysis, linewidth, self-diffusion coefficients); site-directed mutagenesis of proline residues; 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 1alpha (EF-1alpha) that binds to the IFN-gamma gene promoter at the Txk responsive element (-53/-39). Txk phosphorylates EF-1alpha; Txk kinase-dead mutants failed to form this complex. The N-terminal DNA-binding domain of PARP1 is required for complex formation. Upon T cell activation, the complex translocates from cytoplasm to nucleus. A PARP1 inhibitor suppressed IFN-gamma but not IL-4 production. Co-immunoprecipitation; in vitro kinase assay; promoter DNA-binding assay; confocal immunofluorescence; PARP1 inhibitor (PJ34) treatment; kinase-dead and domain-deletion mutants Clinical and experimental immunology High 17177976
2006 Combined loss of Itk and Rlk in mice leads to absence of conventional CD8+ T cells and their replacement by innate-type CD8+ T cells that are CD44hi, CD122+, NK1.1+, produce IFN-gamma directly ex vivo, and are IL-15-dependent. This is accompanied by increased eomesodermin transcription, indicating that Itk and Rlk normally suppress an innate CD8+ T cell developmental program. Itk-/- and Rlk-/-Itk-/- mouse genetic analysis; flow cytometry; cytokine production assays; transcription factor expression analysis Immunity High 16860759 16860760
2008 Combined Itk/Rlk deficiency causes a ~7-fold reduction in invariant NKT cell numbers and a more severe block in NKT cell maturation compared to Itk deficiency alone. Itk-/-/Rlk-/- NKT cells produce little cytokine and show enhanced cell death, correlating with reduced CD122 (IL-2R/IL-15Rβ) and T-bet expression, showing that Rlk contributes to terminal NKT cell maturation and survival. Itk-/- and Itk/Rlk-/- mouse analysis; flow cytometry; in vivo cytokine production assays; cell death assays Journal of immunology Medium 18292523
2008 Txk-null CD4+ T cells produce both Th1 and Th2 cytokines equivalently to wild-type cells, and a Txk transgene expressed at Itk levels fully rescues Th2 responses (allergic asthma, lung granuloma) in Itk-/- mice without notable IFN-gamma enhancement, demonstrating that Itk and Txk do not have distinct signaling specificities but differ in their expression pattern (Txk preferentially in Th1, Itk in both). Txk-null mice; Itk-/- mice bearing Txk transgene; two Th2 disease models (oxazolone asthma, schistosome egg granuloma); cytokine ELISA; flow cytometry Journal of immunology High 18941202
2015 The covalent inhibitor PRN694 binds to cysteine 350 of RLK/TXK (and cysteine 442 of ITK) at the ATP-binding site of the kinase domain, blocking kinase activity with extended target residence time. This inhibits TCR-induced T cell proliferation, proinflammatory cytokine production, and Th17 activation. Molecular modeling; covalent kinase activity assay; in vitro T cell proliferation and cytokine assays; selectivity profiling across TEC family The Journal of biological chemistry Medium 25593320
2015 SH3 domain of TXK interacts with the conserved PxxPxxP SH3-binding motif of the PRRSV nucleocapsid protein, and disruption of proline residues within this motif significantly reduced TXK-N protein interaction. Co-immunoprecipitation; site-directed mutagenesis of PxxP motifs; fluorescent tag steric-hindrance assay Virus research Low 25882913
1994 TXK cDNA encodes a novel cytoplasmic tyrosine kinase primarily expressed in T cells and some myeloid cell lines. Unlike other Tec family members (BTK, ITK, TEC), TXK lacks a pleckstrin homology domain, a Gap1 homology domain, and a steroid hormone receptor homology region in its N-terminal region, but shares SH3, SH2, and kinase catalytic domains. The TXK gene maps to chromosome 4p12. cDNA cloning and sequencing; Northern blot expression analysis; chromosomal mapping by in situ hybridization Human molecular genetics Medium 7951233
1996 The human TXK gene contains 15 exons with strong exon-intron organizational homology to BTK. TXK maps to chromosome 4p12 in close physical linkage (~1.5 kb intergenic region) with the TEC gene, suggesting potential for coordinate cis-regulation of these two Tec family kinases expressed in different hematopoietic lineages. Genomic cloning; restriction mapping; sequencing; chromosomal mapping Oncogene Low 8632917
2006 Itk and Rlk deficiency impairs TCR-dependent signaling in CD8+ T cells, causing defects in PLC-gamma1, p38, and ERK activation, calcium flux, and cytokine production in vitro, and reduced expansion and effector cytokine production during viral infection in vivo. These defects could not be rescued by CD4+ T cell help. Itk-/- and Itk-/-Rlk-/- mice; TCR signaling assays (PLCgamma1, p38, ERK, calcium); viral infection model; adoptive transfer Journal of immunology Medium 16424186

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.) 311 10213685
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 238 11340625
2011 The RLK/Pelle family of kinases. The Plant journal : for cell and molecular biology 178 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 140 28173747
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 98 23198823
2016 Evolutionary Dynamics of the Leucine-Rich Repeat Receptor-Like Kinase (LRR-RLK) Subfamily in Angiosperms. Plant physiology 94 26773008
2008 The Tec kinases Itk and Rlk regulate NKT cell maturation, cytokine production, and survival. Journal of immunology (Baltimore, Md. : 1950) 94 18292523
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
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 71 10523612
2020 Structural evolution drives diversification of the large LRR-RLK gene family. The New phytologist 67 31990988
2009 The Tec kinases Itk and Rlk regulate conventional versus innate T-cell development. Immunological reviews 64 19290924
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
2011 Tec family kinases Itk and Rlk / Txk in T lymphocytes: cross-regulation of cytokine production and T-cell fates. The FEBS journal 63 21362139
1998 Challenges in understanding RLK function. Current opinion in plant biology 59 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 51 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 45 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 43 34583419
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 43 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
2020 The LRR-RLK Protein HSL3 Regulates Stomatal Closure and the Drought Stress Response by Modulating Hydrogen Peroxide Homeostasis. Frontiers in plant science 39 33329622
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 39 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
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 37 30150583
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
2016 LRR-RLK family from two Citrus species: genome-wide identification and evolutionary aspects. BMC genomics 35 27515968
2008 Selective expression rather than specific function of Txk and Itk regulate Th1 and Th2 responses. Journal of immunology (Baltimore, Md. : 1950) 35 18941202
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 34 37127571
2001 Requirements for activation and RAFT localization of the T-lymphocyte kinase Rlk/Txk. BMC immunology 34 11353545
2015 A Small Molecule Inhibitor of ITK and RLK Impairs Th1 Differentiation and Prevents Colitis Disease Progression. Journal of immunology (Baltimore, Md. : 1950) 30 26466958
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
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 27 34626033
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
2020 Computational identification of receptor-like kinases "RLK" and receptor-like proteins "RLP" in legumes. BMC genomics 25 32620079
2018 Genome-Wide Analysis of LRR-RLK Gene Family in Four Gossypium Species and Expression Analysis during Cotton Development and Stress Responses. Genes 25 30501109
2017 A deletion affecting an LRR-RLK gene co-segregates with the fruit flat shape trait in peach. Scientific reports 25 28751691
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 22 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 22 34698114
1992 tkl is the avian homolog of the mammalian lck tyrosine protein kinase gene. Molecular and cellular biology 22 1545804
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
2024 An LRR-RLK protein modulates drought- and salt-stress responses in maize. Journal of genetics and genomics = Yi chuan xue bao 17 39547547
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
2007 Role of Txk, a member of the Tec family of tyrosine kinases, in immune-inflammatory diseases. International reviews of immunology 16 18027204
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 15 33193500
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 15 29468273
2017 ITK and RLK Inhibitor PRN694 Improves Skin Disease in Two Mouse Models of Psoriasis. The Journal of investigative dermatology 15 29129599
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
2022 Spatial range, temporal span, and promiscuity of CLE-RLK signaling. Frontiers in plant science 14 36092449
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) 14 32899802
2019 Genome-wide in silico identification of LysM-RLK genes in potato (Solanum tuberosum L.). Molecular biology reports 14 31317454
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
1984 Fate and structure of DNA microinjected into mouse TK-L cells. Experimental cell research 14 6734747
2020 SGT1 is not required for plant LRR-RLK-mediated immunity. Molecular plant pathology 13 33174685
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
2021 Orthology and synteny analysis of receptor-like kinases "RLK" and receptor-like proteins "RLP" in legumes. BMC genomics 12 33568053
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
2023 Genome-wide analysis and characterization of the LRR-RLK gene family provides insights into anthracnose resistance in common bean. Scientific reports 11 37596307
2017 Root cone angle is enlarged in docs1 LRR-RLK mutants in rice. Rice (New York, N.Y.) 11 29247303
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
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 10 35033836
2018 The overexpression of RXam1, a cassava gene coding for an RLK, confers disease resistance to Xanthomonas axonopodis pv. manihotis. Planta 10 29453662
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 Differential expansion and retention patterns of LRR-RLK genes across plant evolution. Plant direct 9 38145254
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 Recognition of Pep-13/25 MAMPs of Phytophthora localizes to an RLK locus in Solanum microdontum. Frontiers in plant science 8 36714772
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
2024 Characterization, evolution, and abiotic stress responses of leucine-rich repeat receptor-like protein kinases (LRR-RLK) in Liriodendron chinense. BMC genomics 7 39085785
2023 Genome-wide identification and analysis of wheat LRR-RLK family genes following Chinese wheat mosaic virus infection. Frontiers in plant science 7 36733595
2023 Genetic analysis of resistance to bean leaf crumple virus identifies a candidate LRR-RLK gene. The Plant journal : for cell and molecular biology 6 35574650
2015 Genome-Wide Identification and Characterization of the LRR-RLK Gene Family in Two Vernicia Species. International journal of genomics 6 26783513
2023 Genome-Wide Identification of the Soybean LysM-RLK Family Genes and Its Nitrogen Response. International journal of molecular sciences 5 37686427
2020 Identification of a Novel NtLRR-RLK and Biological Pathways That Contribute to Tolerance of TMV in Nicotiana tabacum. Molecular plant-microbe interactions : MPMI 5 32196398
2019 Structural Variations in LysM Domains of LysM-RLK PsK1 May Result in a Different Effect on Pea⁻Rhizobial Symbiosis Development. International journal of molecular sciences 5 30939810

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