ArticleMolecular and cellular biology2002
The pleckstrin homology (PH) domain-interacting protein couples the insulin receptor substrate 1 PH domain to insulin signaling pathways leading to mitogenesis and GLUT4 translocation.
Article in Molecular and cellular biology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 57 citations in OpenAlex.
- Differential phosphorylation of PHIP phosphopeptides with implications in insulin signaling.BMC molecular and cell biology · 2026Article
- Sleep-Disordered Breathing in Chung-Jansen Syndrome.International journal of molecular sciences · 2026Article
- Modeling genotype-by-environment interactions across climatic conditions reveals environment-specific genomic regions and candidate genes underlying feed efficiency traits in tropical beef cattle.Scientific reports · 2026Article
- Novel Insights: A Novel PHIP Variant in a Family with Severe Early-Onset Obesity.Hormone research in paediatrics · 2026Article
- Clinical exome sequencing efficacy and phenotypic expansions involving non-isolated congenital anomalies of kidney and urinary tract (CAKUT+).European journal of human genetics : EJHG · 2025Article
- A new link in the leukemia genetic puzzle.Genes & development · 2025Review
- The health impacts and genetic architecture of food liking in cardio-metabolic diseases.Nature communications · 2025Article
- Human skeletal muscle fiber heterogeneity beyond myosin heavy chains.Nature communications · 2025Article
- Broadening theChildren (Basel, Switzerland) · 2024Article
- RepID as a potential biomarker and therapeutic target for lung neuroendocrine tumor.Scientific reports · 2024Article
- The detection of a strong episignature for Chung-Jansen syndrome, partially overlapping with Börjeson-Forssman-Lehmann and White-Kernohan syndromes.Human genetics · 2024Article
- Clinical phenotypes of individuals with Chung-Jansen syndrome across age groups.American journal of medical genetics. Part A · 2024Article
- Gene expression in notochord and nuclei pulposi: a study of gene families across the chordate phylum.BMC ecology and evolution · 2023Article
- Article
- DCAF14 promotes stalled fork stability to maintain genome integrity.Cell reports · 2021Article
- The replication initiation determinant protein (RepID) modulates replication by recruiting CUL4 to chromatin.Nature communications · 2018Article
- A genotype-first approach identifies an intellectual disability-overweight syndrome caused by PHIP haploinsufficiency.European journal of human genetics : EJHG · 2018Article
- De novoCold Spring Harbor molecular case studies · 2016Article
- A novel IRS-1-associated protein, DGKζ regulates GLUT4 translocation in 3T3-L1 adipocytes.Scientific reports · 2016Article
- PH motifs in PAR1&2 endow breast cancer growth.Nature communications · 2015Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Receptor-mediated tyrosine phosphorylation of the insulin receptor substrate 1 (IRS-1) is required for the propagation of many of insulin's biological effects. The amino-terminal pleckstrin homology (PH) domain of IRS-1 plays a pivotal role in promoting insulin receptor (IR)-IRS-1 protein interactions. We have recently reported the isolation of a PH domain-interacting protein, PHIP, which selectively binds to the IRS-1 PH domain and is stably associated with IRS-1 in mammalian cells. Here we demonstrate that overexpression of PHIP in fibroblasts enhances insulin-induced transcriptional responses in a mitogen-activated protein kinase-dependent manner. In contrast, a dominant-negative mutant of PHIP (DN-PHIP) was shown to specifically block transcriptional and mitogenic signals elicited by insulin and not serum. In order to examine whether PHIP/IRS-1 complexes participate in the signal transduction pathway linking the IR to GLUT4 traffic in muscle cells, L6 myoblasts stably expressing a myc-tagged GLUT4 construct (L6GLUT4myc) were transfected with either wild-type or dominant-interfering forms of PHIP. Whereas insulin-dependent GLUT4myc membrane translocation was not affected by overexpression of PHIP, DN-PHIP caused a nearly complete inhibition of GLUT4 translocation, in a manner identical to that observed with a dominant-negative mutant of the p85 subunit of phosphatidylinositol 3-kinase (Deltap85). Furthermore, DN-PHIP markedly inhibited insulin-stimulated actin cytoskeletal reorganization, a process required for the productive incorporation of GLUT4 vesicles at the cell surface in L6 cells. Our results are consistent with the hypothesis that PHIP represents a physiological protein ligand of the IRS-1 PH domain, which plays an important role in insulin receptor-mediated mitogenic and metabolic signal transduction.
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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.