Last update 01 Nov 2024

PIP4K2B

Last update 01 Nov 2024

Basic Info

Synonyms

1-phosphatidylinositol 5-phosphate 4-kinase 2-beta, Diphosphoinositide kinase 2-beta, Phosphatidylinositol 5-phosphate 4-kinase type II beta

+ [11]

Introduction

Participates in the biosynthesis of phosphatidylinositol 4,5-bisphosphate (PubMed:9038203, PubMed:26774281). Preferentially utilizes GTP, rather than ATP, for PI(5)P phosphorylation and its activity reflects changes in direct proportion to the physiological GTP concentration (PubMed:26774281). Its GTP-sensing activity is critical for metabolic adaptation (PubMed:26774281). PIP4Ks negatively regulate insulin signaling through a catalytic-independent mechanism. They interact with PIP5Ks and suppress PIP5K-mediated PtdIns(4,5)P2 synthesis and insulin-dependent conversion to PtdIns(3,4,5)P3 (PubMed:31091439).

Drugs associated with PIP4K2B

TM-04-168-03

Target

PIP4K2A x PIP4K2B x PIP4K2C

Mechanism

PIP4K2A inhibitors [+2]

Active Org.-

Originator Org.-

Active Indication-

Inactive Indication-

Drug Highest Phase-

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with PIP4K2B

100 Translational Medicine associated with PIP4K2B

0 Patents (Medical) associated with PIP4K2B

Literatures (Medical) associated with PIP4K2B

01 Aug 2024·European Journal of Pharmacology

Potency and efficacy of pharmacological PIP4K2 inhibitors in acute lymphoblastic leukemia

Article

Author: Machado-Neto, João Agostinho ; Lima, Keli ; Velloso, Elvira Deolinda Rodrigues Pereira ; da Silva, Wellington Fernandes ; Cipelli, Marcella ; Leal, Aline de Medeiros ; Schuringa, Jan Jacob ; Câmara, Niels Olsen Saraiva ; Pereira-Martins, Diego Antonio ; Nogueira, Frederico Lisboa ; Carvalho, Maria Fernanda Lopes ; Nardinelli, Luciana ; Bendit, Israel ; Cavaglieri, Rita de Cássia ; Rego, Eduardo Magalhães

Acute lymphoblastic leukemia (ALL), a complex malignancy, displays varying expression profiles of PIP4K2-related genes in adult patients. While PIP4K2A expression is elevated in ALL bone marrow cells compared to healthy bone marrow cells, PIP4K2B is downregulated, and PIP4K2C remains relatively unchanged. Despite the correlation between increased PIP4K2A expression and increased percentage of peripheral blood blasts, clinical outcomes do not strongly correlate with the expression of these genes. Here we investigated the therapeutic potential of three PIP4K2 inhibitors (THZ-P1-2, a131, and CC260) in ALL cell models. THZ-P1-2 emerges as the most effective inhibitor, inducing cell death and mitochondrial damage while reducing cell viability and metabolism significantly. Comparative analyses highlight the superior efficacy of THZ-P1-2 over a131 and CC260. Notably, THZ-P1-2 uniquely disrupts autophagic flux and inhibits the PI3K/AKT/mTOR pathway, indicating a distinct molecular mechanism. In summary, our findings elucidate the differential expression of PIP4K2-related genes in ALL and underscore the potential role of PIP4K2A in disease pathogenesis. The therapeutic promise of THZ-P1-2 in ALL treatment, along with its distinct effects on cell death mechanisms and signaling pathways, enriches our understanding of PIP4K2's involvement in ALL development and offers targeted therapy prospects.

01 Nov 2023·Molecular biology of the cell

Caveola mechanotransduction reinforces the cortical cytoskeleton to promote epithelial resilience.

Article

Author: Tillu, Vikas ; Eckert, Julia ; Parton, Robert G ; Collins, Brett M ; Brooks, John W ; Yap, Alpha S ; Verma, Suzie

As physical barriers, epithelia must preserve their integrity when challenged by mechanical stresses. Cell-cell junctions linked to the cortical cytoskeleton play key roles in this process, often with mechanotransduction mechanisms that reinforce tissues. Caveolae are mechanosensitive organelles that buffer tension via disassembly. Loss of caveolae, through caveolin-1 or cavin1 depletion, causes activation of PtdIns(4, 5)P₂ signaling, recruitment of FMNL2 formin, and enhanced-cortical actin assembly. How this equates to physiological responses in epithelial cells containing endogenous caveolae is unknown. Here we examined the effect of mechanically inducing acute disassembly of caveolae in epithelia. We show that perturbation of caveolae, through direct mechanical stress, reinforces the actin cortex at adherens junctions. Increasing interactions with membrane lipids by introducing multiple phosphatidylserine-binding undecad cavin1 (UC1) repeat domains into cavin1 rendered caveolae more stable to mechanical stimuli. This molecular stabilization blocked cortical reinforcement in response to mechanical stress. Cortical reinforcement elicited by the mechanically induced disassembly of caveolae increased epithelial resilience against tensile stresses. These findings identify the actin cortex as a target of caveola mechanotransduction that contributes to epithelial integrity.

29 Jun 2023·Microorganisms

Investigating the Effects of Alltech Crop Science (ACS) Products on Plant Defence against Root-Knot Nematode Infestation.

Article

Author: Kakouli-Duarte, Thomais ; Singh, Ankit ; Pulavarty, Anusha ; Horgan, Karina ; Young, Kira

Two formulations of Alltech Crop Science products (ACS), a proprietary blend of fermentation products and plant extracts with micronutrients (ACS5075), and a microbial based product (ACS3048), were tested to understand (1) their impact on the tomato plant immune response and (2) whether they are priming a resistance response in plants against root knot nematodes (RKN). Research findings reported previously indicate that tomato plants pre-treated with ACS5075 and ACS3048 were found less sensitive to Meloidogyne javanica infection. In the current study, the expression of six defence-related genes (PR-1, PR-3, PR-5T, ACO, CAT and JERF 3), relative to a housekeeping gene, were monitored via RT-PCR. Results suggest that the treatment with ACS5075 enhanced ACO and PR-1 gene expression levels, both post- treatment and post-infection with M. javanica. Reduced M. javanica infestation that was reported in the previous study could be attributed to the increased expression of these genes in the ACS5075-treated plants. Tomato plants treated with ACS3048, but without RKN infection, also demonstrated higher levels of ACO and PR-1 gene expression. Subsequently, 2D-gel electrophoresis was performed to study the differential protein expression in leaf tissues of treated tomato plants in an effort to elucidate a possible mechanism of action for these products. Protein spot 1 was identified as 'disease resistance protein RPP13-like', protein spot 2 as 'phosphatidylinositol 4-phosphate 5-kinase 2', spot 3 as 'protein SABRE like' and protein spot 4 as 'uncharacterized protein'. Overall research findings indicate that the ACS products could be used as plant immunity-boosting agents, as they play a significant role in the expression of certain genes and proteins associated with plant defence.

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PIP4K2B

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