ArticleOncogene1999
Identification of a chromosome 3p14.3-21.1 gene, APPL, encoding an adaptor molecule that interacts with the oncoprotein-serine/threonine kinase AKT2.
Article in Oncogene, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.
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Who cites it
104 citing papers in PubMed, 205 citations in OpenAlex.
- APPL1 concentration as a potential biomarker in early-onset preeclampsia: correlations with adiponectin-leptin dysregulation and adverse neonatal outcomes.BMC pregnancy and childbirth · 2025Article
- Increased Neuronal Expression of the Early Endosomal Adaptor APPL1 Replicates Alzheimer's Disease-Related Endosomal and Synaptic Dysfunction with Cholinergic Neurodegeneration.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Endosomal HAntioxidants (Basel, Switzerland) · 2025Article
- Adiponectin and Adiponectin Receptors in Atherosclerosis.Endocrine reviews · 2025Review
- Assessment of pathogenicity and functional characterization ofWorld journal of diabetes · 2024Article
- Review
- The Role of Adipokines in the Pathogenesis of Psoriasis.International journal of molecular sciences · 2023Review
- Integrated transcriptome analysis identifies APPL1/RPS6KB2/GALK1 as immune-related metastasis factors in breast cancer.Open medicine (Warsaw, Poland) · 2023Article
- Participation of OCRL1, and APPL1, in the expression, proteolysis, phosphorylation and endosomal trafficking of megalin: Implications for Lowe Syndrome.Frontiers in cell and developmental biology · 2022Article
- Endosomes as Signaling Platforms for IL-6 Family Cytokine Receptors.Frontiers in cell and developmental biology · 2021Review
- Membrane progesterone receptor induces meiosis in Xenopus oocytes through endocytosis into signaling endosomes and interaction with APPL1 and Akt2.PLoS biology · 2020Article
- PTEN: Bridging Endocytosis and Signaling.Cold Spring Harbor perspectives in medicine · 2020Review
- Rab5c-mediated endocytic trafficking regulates hematopoietic stem and progenitor cell development via Notch and AKT signaling.PLoS biology · 2020Article
- Insulin and adipokine signaling and their cross-regulation in postmortem human brain.Neurobiology of aging · 2019Article
- Lysosome Positioning Influences mTORC2 and AKT Signaling.Molecular cell · 2019Article
- Mutant p53 amplifies a dynamin-1/APPL1 endosome feedback loop that regulates recycling and migration.The Journal of cell biology · 2019Article
- Metabolic Messengers: Adiponectin.Nature metabolism · 2019Review
- Retrograde transport of Akt by a neuronal Rab5-APPL1 endosome.Scientific reports · 2019Article
- Akt-ing Up Just About Everywhere: Compartment-Specific Akt Activation and Function in Receptor Tyrosine Kinase Signaling.Frontiers in cell and developmental biology · 2019Review
- ARAP2 inhibits Akt independently of its effects on focal adhesions.Biology of the cell · 2018Article
44 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
AKT2 is a serine/threonine kinase implicated in human ovarian and pancreatic cancers. AKT2 is activated by a variety of growth factors and insulin via phosphatidylinositol 3-kinase (PI3K). However, its normal cellular role is not well understood. To gain insight into the function of AKT2, we performed yeast two-hybrid system to screen for interacting proteins. Using this technique, we identified a novel interactor, designated APPL, which contains a pleckstrin homology (PH) domain, a phosphotyrosine binding (PTB) domain and a leucine zipper, classes of motifs defined in signaling molecules as functional interaction domains with specific targets. The PH domain of APPL shows similarity to those found in GTPase-activating proteins such as oligophrenin-1 and Graf, whereas its PTB domain exhibits homology with CED-6, an adaptor protein that promotes engulfment of apoptotic cells, and IB1, a transactivator of the GLUT2 gene. APPL is highly expressed in skeletal muscle, heart, ovary and pancreas, tissues in which AKT2 mRNA is abundant. APPL interacts with the inactive form of AKT2; moreover, APPL binds to the PI3K catalytic subunit, p110alpha. These data suggest that APPL is an adaptor that may tether inactive AKT2 to p110alpha in the cytoplasm and thereby may expedite recruitment of AKT2 and p110alpha to the cell membrane upon mitogenic stimulation. Furthermore, the APPL gene was mapped to human chromosome 3p14.3-p21.1, where deletions and other rearrangements have often been reported in a variety of tumor types. The identification of APPL may facilitate further analysis of the physiological and oncogenic activities of AKT2.
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Registered trials
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.