ArticleThe Journal of biological chemistry2015
Phosphatidylinositol Phosphate 5-Kinase Iγ and Phosphoinositide 3-Kinase/Akt Signaling Couple to Promote Oncogenic Growth.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 46 citations in OpenAlex.
- PIPKIγ promotes non-homologous end joining through LIG4 to enhance radiotherapy resistance in triple-negative breast cancer.Cell death & disease · 2025Article
- Phosphoinositide kinases in cancer: from molecular mechanisms to therapeutic opportunities.Nature reviews. Cancer · 2025Review
- PIP5Kγ Mediates PI(4,5)P2/Merlin/LATS1 Signaling Activation and Interplays with Hsc70 in Hippo-YAP Pathway Regulation.International journal of molecular sciences · 2023Article
- Regulation of Cell Adhesion and Migration via Microtubule Cytoskeleton Organization, Cell Polarity, and Phosphoinositide Signaling.Biomolecules · 2023Review
- PI(4,5)PScience advances · 2023Article
- Lipid kinases PIP5Ks and PIP4Ks: potential drug targets for breast cancer.Frontiers in oncology · 2023Review
- Role of LGMN in tumor development and its progression and connection with the tumor microenvironment.Frontiers in molecular biosciences · 2023Review
- The role of K63-linked polyubiquitin in several types of autophagy.Biologia futura · 2022Review
- A Comparative Study to Visualize PtdIns(4,5) P2 and PtdIns(3,4,5) P3 in MDA-MB-231 Breast Cancer Cell Line.Reports of biochemistry & molecular biology · 2022Article
- Targeting cancer-specific metabolic pathways for developing novel cancer therapeutics.Frontiers in immunology · 2022Review
- Taxifolin as a Major Bioactive Compound in the Vasorelaxant Effect of Different Pigmented Rice Bran Extracts.Frontiers in pharmacology · 2022Article
- Modulatory Effect of 4-(methylthio)butyl Isothiocyanate Isolated FromFrontiers in pharmacology · 2021Article
- PTEN and Other PtdIns(3,4,5)PInternational journal of molecular sciences · 2020Review
- Phosphatidylinositol-3-OH kinase signalling is spatially organized at endosomal compartments by microtubule-associated protein 4.Nature cell biology · 2020Article
- Phosphoinositide lipids in primary cilia biology.The Biochemical journal · 2020Review
- PtdIns(4,5)P2 and PtdIns(3,4,5)P3 dynamics during focal adhesions assembly and disassembly in a cancer cell line.Turkish journal of biology = Turk biyoloji dergisi · 2020Article
- Type Iγ phosphatidylinositol phosphate kinase promotes tumor growth by facilitating Warburg effect in colorectal cancer.EBioMedicine · 2019Article
- PIPKIJournal of immunology research · 2019Article
- Effect ofBioscience reports · 2018Article
- Oncogene Delta/Notch-Like EGF-Related Receptor Promotes Cell Proliferation, Invasion, and Migration in Hepatocellular Carcinoma and Predicts a Poor Prognosis.Cancer biotherapy & radiopharmaceuticals · 2018Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The assembly of signaling complexes at the plasma membrane is required for the initiation and propagation of cellular signaling upon cell activation. The class I PI3K and the serine/threonine-specific protein kinase Akt signaling pathways (PI3K/Akt) are often activated in tumors. These pathways are initiated by the generation of phosphatidylinositol 3,4,5-triphosphate (PIP3) by PI3K-mediated phosphorylation of phosphatidylinositol 4,5-biphosphate (PIP2), synthesized by phosphatidylinositol 4-phosphate 5-kinase (PIPKI) enzymes. The mechanism of how tumor cells recruit and organize the PIP2-synthesizing enzymes with PI3K in the plasma membrane for activation of PI3K/Akt signaling is not defined. Here, we demonstrated a role for the phosphatidylinositol 4-phosphate 5-kinase Iγ (PIPKIγ) in PI3K/Akt signaling. PIPKIγ is overexpressed in triple-negative breast cancers. Loss of PIPKIγ or its focal adhesion-targeting variant, PIPKIγi2, impaired PI3K/Akt activation upon stimulation with growth factors or extracellular matrix proteins in different tumor cells. PIPKIγi2 assembles into a complex containing Src and PI3K; Src was required for the recruitment of PI3K enzyme into the complex. PIPKIγi2 interaction with Src and its lipid kinase activity were required for promoting PI3K/Akt signaling. These results define a mechanism by which PIPKIγi2 and PI3K are integrated into a complex regulated by Src, resulting in the spatial generation of PIP2, which is the substrate PI3K required for PIP3 generation and subsequent Akt activation. This study elucidates the mechanism by which PIP2-generating enzyme controls Akt activation upstream of a PI3K enzyme. This pathway may represent a signaling nexus required for the survival and growth of metastasizing and circulating tumor cells in vivo.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.