Ask about this productRelated genes to: PIP5KL1 antibody
- Gene:
- PIP5KL1 NIH gene
- Name:
- phosphatidylinositol-4-phosphate 5-kinase like 1
- Previous symbol:
- -
- Synonyms:
- bA203J24.5, MGC46424
- Chromosome:
- 9q34.11
- Locus Type:
- gene with protein product
- Date approved:
- 2004-02-17
- Date modifiied:
- 2016-10-05
Related products to: PIP5KL1 antibody
Related articles to: PIP5KL1 antibody
- Dogs are the only large mammals, besides humans, that develop spontaneous prostate cancer, which has a poor prognosis and limited treatment efficacy. Considering the central role of mammalian target of rapamycin (mTOR) in carcinogenesis, the use of rapamycin, an mTOR inhibitor, has attracted considerable attention. In this study, we performed gene expression microarray analyses of normal canine prostate and prostate carcinoma cells. Among the 6,270 differentially expressed genes revealed in the transcriptome, 3,242 were upregulated and 3,028 were downregulated, and were related to phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway activation, as confirmed by enrichment analysis. Among the genes involved in this pathway, we found increased expression levels of FKBP1A, FKBP1B, AKT1S1, PDK2, PIP5K1 and PIP5KL1 in canine prostate cancer cells compared with normal prostate cells. We also treated two canine prostate cancer cell lines (PC1 and PC2) with rapamycin in vitro (6, 10 and 12 μM) for 24 h and observed a dose-dependent decrease in cell viability. Our results indicate that rapamycin significantly increased AKT transcript levels in both cell lines, indicating resistance to treatment. However, mTOR and 4E-BP1 expression were downregulated after rapamycin treatment. We suggest that mTOR inhibition is a potential treatment of choice for canine prostate cancer, which may guide and contribute to future prostate carcinoma clinical trials. However, the acquisition of resistance to treatment remains a challenge, and precision medicine may help overcome this problem. - Source: PubMed
Publication date: 2025/05/05
Kobayashi Priscila ELainetti Patrícia FLeis-Filho Antonio FDelella Flávia KVicente Igor S TFonseca-Alves Carlos ELaufer-Amorim Renée - The LDL receptor-related protein 1 (LRP1) is a multifunctional transmembrane protein with endocytosis and signal transduction functions. Previous studies have shown that hepatic LRP1 deficiency exacerbates diet-induced steatohepatitis and insulin resistance via mechanisms related to increased lysosome and mitochondria permeability and dysfunction. The current study examined the impact of LRP1 deficiency on mitochondrial function in the liver. Hepatocytes isolated from liver-specific LRP1 knockout (hLrp1) mice showed reduced oxygen consumption compared with control mouse hepatocytes. The mitochondria in hLrp1 mouse livers have an abnormal morphology and their membranes contain significantly less anionic phospholipids, including lower levels of phosphatidylethanolamine and cardiolipin that increase mitochondrial fission and impair fusion. Additional studies showed that LRP1 complexes with phosphatidylinositol 4-phosphate 5-kinase like protein-1 (PIP5KL1) and phosphatidylinositol 4-phosphate 5-kinase-1β (PIP5K1β). The absence of LRP1 reduces the levels of both PIP5KL1 and PIP5K1β in the plasma membrane and also lowers phosphatidylinositol(4,5) bisphosphate (PI(4,5)P) levels in hepatocytes. These data indicate that LRP1 recruits PIP5KL1 and PIP5K1β to the plasma membrane for PI(4,5)P biosynthesis. The lack of LRP1 reduces lipid kinase expression, leading to lower PI(4,5)P levels, thereby decreasing the availability of this lipid metabolite in the cardiolipin biosynthesis pathway to cause cardiolipin reduction and the impairment in mitochondria homeostasis. Taken together, the current study identifies another signaling mechanism by which LRP1 regulates cell functions: binding and recruitment of PIP5KL1 and PIP5K1β to the membrane for PI(4,5)P synthesis. In addition, it highlights the importance of this mechanism for maintaining the integrity and functions of intracellular organelles. - Source: PubMed
Publication date: 2021/02/03
Chinnarasu SivaprakasamAlogaili FawziBove Kevin EJaeschke AnjaHui David Y - The generation of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P) by phosphatidylinositol 4-phosphate 5-kinases (PIP5Ks) is essential for many functions including control of the cytoskeleton, signal transduction, and endocytosis. Due to its presence in the plasma membrane and anionic charge, PtdIns(4,5)P, together with phosphatidylserine, provide the inner leaflet of the plasma membrane with a negative surface charge. This negative charge helps to define the identity of the plasma membrane, as it serves to recruit or regulate a multitude of peripheral and membrane proteins that contain polybasic domains or patches. Here, we determine that the phosphatidylinositol 4-phosphate 5-kinase homolog (PIPKH) alters the subcellular distribution of PtdIns(4,5)P by re-localizing the three PIP5Ks to endomembranes. We find a redistribution of the PIP5K family members to endomembrane structures upon PIPKH overexpression that is accompanied by accumulation of PtdIns(4,5)P and phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P). PIP5Ks are targeted to membranes in part due to electrostatic interactions; however, the interaction between PIPKH and PIP5K is maintained following hydrolysis of PtdIns(4,5)P. Expression of PIPKH did not impair bulk endocytosis as monitored by FM4-64 uptake but did result in clustering of FM4-64 positive endosomes. Finally, we demonstrate that accumulation of polyphosphoinositides increases the negative surface charge of endosomes and in turn, leads to relocalization of surface charge probes as well as the polycationic proteins K-Ras and Rac1. - Source: PubMed
Publication date: 2019/10/15
Yang YanboPark MiriamMaekawa MasashiFairn Gregory D - PIP5KL1 (phosphatidylinositol-4-phosphate 5-kinase-like 1), the fourth member of PIP5Ks (phosphatidylinositol-4-phosphate 5-kinases) type I, acts as a scaffold for localization and activation of PIP5Ks, which in turn regulate numerous cellular processes. However, the role of PIP5KL1 in the development of human cancer is poorly studied. In this study, we established a stable clone of PIP5KL1 overexpressing human cervical cancer HeLa cells. RT-PCR (reverse transcription-polymerase chain reaction) and Western immunoblot analysis were performed to testify the mRNA and protein levels of PIP5KL1 in HeLa cells. The effect of PIP5KL1 overexpression on in vitro cell growth was assessed by measuring cell proliferation and migration. The athymic nude mouse model was used to examine the effects of PIP5KL1 on tumour growth in vivo. Stable transfection of PIP5KL1 induced a significant increase in expression of both mRNA and protein levels and consequent robust inhibition of proliferation (P<0.05) and migration (P<0.05) of HeLa cells. Overexpression of PIP5KL1 significantly suppressed the growth of HeLa xenograft tumours in the flanks of nude mice. Taken together, these studies indicate a functional negative correlation between elevated levels of PIP5KL1 and the development of human cervical cancer, suggesting that PIP5KL1 overexpression may suppress cervical cancer formation. - Source: PubMed
Publication date: 2010/02/22
Shi LanWang KaiZhao MeiYuan XinghuaHuang Changzhi - Phosphatidylinositol-4-phosphate 5-kinase-like 1 (PIP5KL1), the forth member of phosphatidylinositol-4-phosphate 5-kinases (PIPKs) type I, acts as a scaffold for localization and activation of PIPKs, which mediates numerous cellular processes. However, the role of PIP5KL1 in the development of human cancer is still lacking. We therefore examined the expression of PIP5KL1 in human normal and cancer tissues by tissue microarrays (TMAs). Reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence imaging analysis were used to testify the mRNA and protein levels of PIP5KL1 in human gastric cancer cell line (BGC823). The cell proliferation was investigated with 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay. Both wound healing and transwell migration assay were performed to study the cell migration. The phosphorylation of v-akt murine thymoma viral oncogene homolog 1 (AKT1) was determined by western immunoblot analysis. Immunostaining of gastric cancer tissue microarrays revealed a negative correlation between PIP5KL1 overexpression and gastric cancer in situ. Transient transfection PIP5KL1 induced a significant increase expression at both transcriptional and translational levels and consequent robust inhibition of proliferation (P < 0.05) and migration (P < 0.05) of BGC823 cells. Overexpression of PIP5KL1 markedly inhibited (P < 0.05) serum-induced phosphorylation of AKT1. Taken together, these studies indicate a functional negative correlation between elevated levels of PIP5KL1 and the development of human gastric cancer, suggesting that PIP5KL1 overexpression may suppress gastric cancer formation. - Source: PubMed
Publication date: 2009/08/13
Shi LanZhao MeiLuo QingMa Yi-MingZhong Jia-LingYuan Xing-HuaHuang Chang-Zhi