RPS6KA3 & PDPK1 Protein Protein Interaction Antibody Pair
- Known as:
- RPS6KA3 & PDPK1 Protein Protein Interaction Antibody Pair
- Catalog number:
- DI0623
- Product Quantity:
- 1 Set
- Category:
- -
- Supplier:
- Abno
- Gene target:
- RPS6KA3 & PDPK1 Protein Interaction Antibody Pair
Related genes to: RPS6KA3 & PDPK1 Protein Protein Interaction Antibody Pair
- Gene:
- PDPK1 NIH gene
- Name:
- 3-phosphoinositide dependent protein kinase 1
- Previous symbol:
- -
- Synonyms:
- PDK1
- Chromosome:
- 16p13.3
- Locus Type:
- gene with protein product
- Date approved:
- 1998-03-23
- Date modifiied:
- 2015-08-25
- Gene:
- RPS6KA3 NIH gene
- Name:
- ribosomal protein S6 kinase A3
- Previous symbol:
- MRX19, CLS
- Synonyms:
- RSK2, HU-3
- Chromosome:
- Xp22.12
- Locus Type:
- gene with protein product
- Date approved:
- 1994-07-11
- Date modifiied:
- 2018-04-18
Related products to: RPS6KA3 & PDPK1 Protein Protein Interaction Antibody Pair
Related articles to: RPS6KA3 & PDPK1 Protein Protein Interaction Antibody Pair
- Despite the oncogenic roles of the serine/threonine kinase PDPK1 and its key effectors, RSK2 and AKT, their activation status and prognostic significance remain unexamined in B cell lymphomas (BCLs). This study evaluated the phosphorylation states of PDPK1, the RSK2-N-terminal kinase domain (NTKD), and AKT through immunohistochemical analyses of 468 biopsied samples from patients with nine subtypes of MLs, including diffuse large B cell lymphoma (DLBCL) ( = 277) and follicular lymphoma (FL) ( = 121). PDPK1 was frequently phosphorylated in most subtypes, showing 98% in DLBCL and 76% in FL. RSK2-NTKD was phosphorylated in 100% and 69% of DLBCL and FL, respectively. AKT was phosphorylated in 68% and 53% of DLBCL and FL, respectively. Intriguingly, moderate to strong p-RSK2-NTKD expression significantly correlated with poor overall survival in DLBCL, especially in the non-GCB type, but not in FL. These emphasize the PDPK1/RSK2-NTKD pathway as a prognostic marker and a potential therapeutic target in various BCLs. - Source: PubMed
Publication date: 2025/03/25
Onishi AkioMiyagawa-Hayashino AyaOkamoto HaruyaFujino TakahiroTsukamoto TakuMizutani ShinsukeShimura YujiKonishi EiichiKuroda Junya - Multiple myeloma (MM) remains a difficult-to-treat disease even with the latest therapeutic advances due to the complex, overlapping, and heterogeneous cytogenetic, genetic, and molecular abnormalities. To address this challenging problem, we previously identified the universal and critical roles of RSK2 and AKT, the effector signaling molecules downstream of PDPK1, regardless of cytogenetic and genetic profiles. Based on this, in this study, we investigated the anti-myeloma potency of TAS0612, a triple inhibitor against RSK, including RSK2, AKT, and S6K. Treatment with TAS0612 exerted the anti-proliferative effect via cell cycle blockade and the induction of apoptosis in human myeloma-derived cell lines (HMCLs) with diverse cytogenetic and genetic profiles. Ex vivo treatment with TAS0612 also significantly reduced the viability of patient-derived primary myeloma cells with diverse cytogenetic profiles. TAS0612 simultaneously caused the upregulation of several tumor suppressor genes, modulated prognostic genes according to the MMRF CoMMpass data, and downregulated a series of Myc- and mTOR-related genes. Moreover, the combination of TAS0612 with venetoclax (VEN) showed the synergy in inducing apoptosis in HMCLs irrespective of the t(11;14) translocation status. TAS0612 alone and combined with VEN are new potent candidate therapeutic strategies for MM, regardless of cytogenetic/genetic profiles, facilitating its future clinical development. - Source: PubMed
Publication date: 2024/10/22
Okamoto HaruyaMizutani ShinsukeTsukamoto TakuKatsuragawa-Taminishi YokoKawaji-Kanayama YukaMizuhara KentaroMuramatsu AyakoIsa ReikoFujino TakahiroShimura YujiIchikawa KojiKuroda Junya - Mantle cell lymphoma (MCL) is a relatively rare subtype of B-cell non-Hodgkin lymphoma (NHL) that has a poor prognosis despite recent advances in immunochemotherapy and molecular targeted therapeutics against NHL. Therefore, the development of a new therapeutic strategy for MCL is urgently needed. In this study, we show for the first time that 3-phosphoinositide-dependent protein kinase 1 (PDPK1), an oncogenic serine-threonine protein kinase, is commonly expressed in its phosphorylated active form in patient-derived tumor cells of various types of B-cell NHL cells, including diffuse large B-cell lymphoma, follicular lymphoma, and MCL. Blockade of PDPK1 activity by small-molecule inhibitors specific for PDPK1 (BX-912 and GSK2334470) or by RNA interference exerted antiproliferative effects in all four MCL-derived cell lines examined and these growth-inhibitory effects were mediated by both induction of apoptosis and G/M cell cycle blockade. In addition, blockade of PDPK1 led to inactivation of its downstream effector kinase RSK2, but not AKT, suggesting the importance of the PDPK1/RSK2 signaling pathway in the proliferation and survival of MCL cells. Finally, when combined with anticancer agents, including genotoxic agents, a proteasome inhibitor, and a BH3 mimetic in vitro, the PDPK1 inhibitor BX-912 showed additive growth-inhibitory effects against MCL-derived cell lines in most settings. In particular, the combination of BX-912 and ABT-263, a BH3 mimetic, resulted in the enhancement of the induction of apoptosis. In conclusion, our results suggest that PDPK1 is a potential novel therapeutic target in MCL and indicate that clinical development of PDPK1-targeted therapy for MCL is desirable. - Source: PubMed
Publication date: 2017/12/26
Maegawa SaoriChinen YoshiakiShimura YujiTanba KazunaTakimoto TomokoMizuno YoshimiMatsumura-Kimoto YayoiKuwahara-Ota SaekoTsukamoto TakuKobayashi TsutomuHoriike ShigeoTaniwaki MasafumiKuroda Junya - Cytogenetic/molecular heterogeneity is the hallmark of multiple myeloma (MM). However, we recently showed that the serine/threonine kinase PDPK1 and its substrate RPS6KA3 (also termed RSK2) are universally active in MM, and play pivotal roles in myeloma pathophysiology. In this study, we assessed involvement of aberrant miR-375 repression in PDPK1 overexpression in MM. An analysis of plasma cells from 30 pre-malignant monoclonal gammopathies of undetermined significance and 73 MM patients showed a significant decrease in miR-375 expression in patient-derived plasma cells regardless of the clinical stage, compared to normal plasma cells. Introduction of miR-375 reduced PDPK1 expression in human myeloma cell lines (HMCLs), indicating that miR-375 is the dominant regulator of PDPK1 expression. In addition, miR-375 introduction also downregulated IGF1R and JAK2 in HMCLs. CpG islands in the MIR375 promoter were pathologically hypermethylated in all 8 HMCLs examined and in most of 58 patient-derived myeloma cells. Treatment with SGI-110, a hypomethylating agent, and/or trichostatin A, a histone deacetylase inhibitor, increased miR-375 expression, but repressed PDPK1, IGF1R and JAK2 in HMCLs. Collectively, these results show the universal involvement of overlapping epigenetic dysregulation for abnormal miR-375 repression in MM, which is likely to contribute to myelomagenesis and to subsequent myeloma progression by activating oncogenic signalling pathways. - Source: PubMed
Publication date: 2017/04/25
Tatekawa ShotaroChinen YoshiakiRi MasakiNarita TomokoShimura YujiMatsumura-Kimoto YayoiTsukamoto TakuKobayashi TsutomuKawata EriUoshima NobuhikoTaki TomohikoTaniwaki MasafumiHanda HiroshiIida ShinsukeKuroda Junya - This study investigated the role of PDK1 in inflammatory response which is initiated by TNF-α and analyzed the association between PDK1 and RSK2. TNF-α were added into MH7A cells to induce inflammation condition. Through overexpressing or suppressing PDK1 in MH7A cells, the role of PDK1 in cell invasiveness and inflammatory factors was determined. Levels of MMPs protein and inflammatory cytokines were assessed with PDK1 siRNA and TNF-α treatment. Inhibition of RSK2 was used to investigate the function of RSK2 on PDK1-induced inflammation. The phosphorylation of RSK2 was detected when PDK1 was inhibited. Luciferase reporter assay was performed to detect the transcriptional activity of NF-κB. We found highly expressed PDK1 could promote cell invasion and secretion of IL-1β and IL-6 in MH7A cells. Inhibition of RSK2 reduced the PDK1-induced cell invasion and cytokines secretion in MH7A cells. In response to TNF-α, PDK1 could phosphorylate RSK2 and activated RSK2, then promoting the activation of NF-κB. This may be a possible therapeutic option of rheumatoid arthritis. - Source: PubMed
Publication date: 2016/11/01
Sun ChiSun YuJiang DingjunBao GuofengZhu XinhuiXu DaweiWang YouhuaCui Zhiming