KSR2

Last update 08 May 2025

Basic Info

Synonyms

FLJ25965, hKSR2, kinase suppressor of ras 2

+ [1]

Introduction

Location-regulated scaffold connecting MEK to RAF. Has very low protein kinase activity and can phosphorylate MAP2K1 at several Ser and Thr residues with very low efficiency (in vitro). Acts as MAP2K1/MEK1-dependent allosteric activator of BRAF; upon binding to MAP2K1/MEK1, dimerizes with BRAF and promotes BRAF-mediated phosphorylation of MAP2K1/MEK1 (PubMed:29433126). Interaction with BRAF enhances KSR2-mediated phosphorylation of MAP2K1 (in vitro). Blocks MAP3K8 kinase activity and MAP3K8-mediated signaling. Acts as a negative regulator of MAP3K3-mediated activation of ERK, JNK and NF-kappa-B pathways, inhibiting MAP3K3-mediated interleukin-8 production.

100 Clinical Results associated with KSR2

100 Translational Medicine associated with KSR2

0 Patents (Medical) associated with KSR2

Literatures (Medical) associated with KSR2

01 Mar 2025·Modern Pathology

Characterizing Nodal Gamma-Delta T-Cell Lymphoma: Clinicopathological and Molecular Insights

Article

Author: Eren, Ozgur Can ; Sohani, Aliyah R ; Au-Yeung, Rex K H ; Lim, Jing Quan ; Ng, Siok-Bian ; Dogan, Ahmet ; Kumar, Jyoti ; Quintanilla-Martinez, Leticia ; Bosch-Schips, Jan ; Climent, Fina ; Oon, Ming Liang ; Ong, Choon-Kiat ; Hutchison, Bailey

Peripheral T-cell lymphomas with gamma-delta phenotype (GDTCL) are rare lymphoid malignancies. Beyond the well-recognized entities of extranodal lymphomas with gamma-delta phenotype as defined by the fifth edition of the World Health Organization Classification of Hematolymphoid Tumors and 2022 International Consensus Classification, there is a group of poorly defined gamma-delta T-cell lymphomas with predominantly nodal presentation, termed as nodal GDTCL (nGDTCL). In this study, we present a series of 12 cases of Epstein-Barr virus-negative nGDTCL, highlighting the clinical, histopathological, and molecular features of this rare entity. Seven cases reported in the literature were included in the analysis. Of the 12 cases, nGDTCL shows an increased incidence in elderly men, with a median age of 65.5 years. All cases presented primarily with enlarged lymph nodes, and 4 cases (4/12, 33.3%) showed involvement of extranodal sites, including skin, liver, spleen, and bone marrow. Histologically, 9 cases showed a diffuse and monomorphic proliferation of mostly medium-to-large lymphoid cells, whereas 3 cases demonstrated lymphoepithelioid morphology. All cases (12/12, 100%) were positive for CD3 and TCRγδ. CD4, CD8, and CD56 were positive in 66.7% (8/12), 25% (3/12), and 8.3% (1/11) of cases, respectively. Most cases (8/12, 66.7%) showed a noncytotoxic phenotype. Using immunohistochemistry, the majority of cases (6/8, 75.0%) belonged to the peripheral T-cell lymphoma-GATA3 subtype with GATA3 and/or CCR4 expression and a noncytotoxic CD4-positive phenotype. Two cases (2/8, 25%) belonged to the peripheral T-cell lymphoma-TBX21 subtype, of which 1 displayed a cytotoxic CD8-positive phenotype. Next-generation sequencing was performed in 9 cases, and TP53 mutation was detected in 66.7% (6/9) of the cases. Mutations of ATM and KSR2 were identified in 2 cases each. It remains uncertain whether nGDTCL represents a distinct entity, and further studies are needed for better characterization. Nonetheless, nodal-based GDTCL should be distinguished from secondary nodal involvement by other extranodal GDTCL and Epstein-Barr virus-positive T/NK-cell lymphoproliferative diseases.

01 Mar 2025·Journal of Ethnopharmacology

Zhichuanling injection improves bronchial asthma by attenuation airway inflammation and epithelia-mesenchymal transition

Article

Author: Liang, Huaduan ; Cao, Zhengyu ; Song, Mengmeng ; Zhao, Fang ; Niu, Bo ; Chen, Jingyi ; Ren, Kerui ; Xi, Chuchu

ETHNOPHARMACOLOGICAL RELEVANCEZhichuanling (ZCL) Injection, is a compound formulation containing extracts of mahuang (Herba Ephedrae, dried stem or aerial part of Ephedra sinica Stapf), bitter almond (Semen Armeniacae Amarum, seeds of Prunus armeniaca var. sibirica (L.) K. Koch), yangjinhua (flower of Datura metel L.) and Fructus Forsythiae (fruits of Forsythia suspensa (Thunb.) Vahl). Intramuscular injection of ZCL has been used in the clinical practice to control asthma. The aerosol inhalation of ZCL has been shown to be effective on allergic bronchial asthma. However, the underlying mechanisms remain established.AIM OF THE STUDYTo investigate the underling mechanism by which ZCL inhibits the pathogenesis of bronchial asthma.METHODSThe guinea pig tracheal rings and human bronchial epithelial (16HBE) cells were used to assess ZCL's impact on acetylcholine (Ach) induced tracheal contraction, tumor necrosis factor α (TNF-α) induced bronchial inflammation, and transforming growth factor-β1 (TGF-β1) induced airway remodeling. Cell viability and gene expression were assessed using MTT assays, qPCR. RNA-seq (gene expression analysis) was employed to explore the novel mechanisms of ZCL in OVA-induced bronchial asthma.RESULTSIn this study, we found that ZCL reduces Ach-induced contraction of isolated guinea pig trachea, suppress TNF-α-induced interleukin (IL)-1β, IL-6, and IL-8 and TGF-β1-induced E-cadherin, α-SMA, Vimentin, N-cadherin mRNA expression in the 16HBE. Transcriptomic analysis of lung tissue from mice with OVA-induced bronchial asthma suggests that ZCL may alleviate asthma symptoms by modulating BPIFA1, HIF3Α, CTXN3, GRFA3, PPEF1, KSR2, and CDSN.CONCLUSIONZCL alleviates asthma by suppressing tracheal contractions, inflammation, and epithelial-to-mesenchymal transition. ZCL effect on asthma is likely through the upregulation of BPIFA1 expression thus providing the molecular insight for the treatment of asthma. The findings suggest that ZCL holds promise as a asthma therapeutic approach, and further research is needed to explore its full clinical potential. Future studies should focus on optimizing dosage, evaluating long-term efficacy, and investigating potential synergistic effects with existing treatments to enhance asthma management and patient outcomes.

01 Jan 2025·Archives of Endocrinology and Metabolism

Comprehensive microarray analysis for the identification of therapeutic targets within HIF-1α signalling networks in diet-induced obesity via hypothalamic inflammation

Article

Author: Ma, Lijuan ; Guo, Hai ; Duolikun, Dilihumaier ; Yao, Qiaoling

OBJECTIVEA high-fat diet (HFD) significantly contributes to obesity and alters the neurological function of the brain. This study explored the influence of hypoxia-inducible factor (HIF-1) and its downstream molecules on obesity progression in the context of HFD-induced hypothalamic inflammation.MATERIALS AND METHODSUtilizing a bioinformatics approach alongside animal models, targets and pathways related to hypothalamic obesity were identified via network analysis, gene target identification, gene ontology analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and subsequent validation in animal models.RESULTSHIF-1α has the potential to regulate the immune response by promoting immune infiltration and increasing the population of immune cells, particularly memory CD4 T cells, in the hypothalamus, primarily through its influence on ksr2 expression. Additionally, the analysis predicted five drugs capable of enhancing HIF-1-Ksr2 signalling.CONCLUSIONIn conclusion, targeting Ksr2 with specific drugs represents a potential approach for addressing HFD-induced obesity. These novel findings lay the groundwork for developing dietary supplements and therapeutic interventions.

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KSR2

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