ArticleMolecular endocrinology (Baltimore, Md.)2011
Phospholipase C and protein kinase C-β 2 mediate insulin-like growth factor II-dependent sphingosine kinase 1 activation.
Article in Molecular endocrinology (Baltimore, Md.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
- IGF2R: a new player in the IGF2 loop sustaining adrenocortical carcinogenesis.Cell communication and signaling : CCS · 2026Article
- Signaling controversy and future therapeutical perspectives of targeting sphingolipid network in cancer immune editing and resistance to tumor necrosis factor-α immunotherapy.Cell communication and signaling : CCS · 2024Review
- Dysglycemia With Impaired Insulin Secretion After Resection of a High-Molecular-Weight IGF-II-Producing Tumor.JCEM case reports · 2023Article
- A Rheostat of Ceramide and Sphingosine-1-Phosphate as a Determinant of Oxidative Stress-Mediated Kidney Injury.International journal of molecular sciences · 2022Review
- Receptor Tyrosine Kinase Signaling and Targeting in Glioblastoma Multiforme.International journal of molecular sciences · 2021Review
- Cholecalciferol (Vitamin DMolecular neurobiology · 2019Article
- STAT3-mediated IGF-2 secretion in the tumour microenvironment elicits innate resistance to anti-IGF-1R antibody.Nature communications · 2015Article
- Inhibition of Sphingosine Kinase 1 Ameliorates Angiotensin II-Induced Hypertension and Inhibits Transmembrane Calcium Entry via Store-Operated Calcium Channel.Molecular endocrinology (Baltimore, Md.) · 2015Article
- Ceramide-induced apoptosis in renal tubular cells: a role of mitochondria and sphingosine-1-phoshate.International journal of molecular sciences · 2015Review
- Sulfhydration of p66Shc at cysteine59 mediates the antioxidant effect of hydrogen sulfide.Antioxidants & redox signaling · 2014Article
- Cell-surface receptors transactivation mediated by g protein-coupled receptors.International journal of molecular sciences · 2014Review
- Biochemical characterization of individual human glycosylated pro-insulin-like growth factor (IGF)-II and big-IGF-II isoforms associated with cancer.The Journal of biological chemistry · 2013Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
We recently reported that IGF-II binding to the IGF-II/mannose-6-phosphate (M6P) receptor activates the ERK1/2 cascade by triggering sphingosine kinase 1 (SK1)-dependent transactivation of G protein-coupled sphingosine 1-phosphate (S1P) receptors. Here, we investigated the mechanism of IGF-II/M6P receptor-dependent sphingosine kinase 1 (SK1) activation in human embryonic kidney 293 cells. Pretreating cells with protein kinase C (PKC) inhibitor, bisindolylmaleimide-I, abolished IGF-II-stimulated translocation of green fluorescent protein (GFP)-tagged SK1 to the plasma membrane and activation of endogenous SK1, implicating PKC as an upstream regulator of SK1. Using confocal microscopy to examine membrane translocation of GFP-tagged PKCα, β1, β2, δ, and ζ, we found that IGF-II induced rapid, transient, and isoform-specific translocation of GFP-PKCβ2 to the plasma membrane. Immunoblotting of endogenous PKC phosphorylation confirmed PKCβ2 activation in response to IGF-II. Similarly, IGF-II stimulation caused persistent membrane translocation of the kinase-deficient GFP-PKCβ2 (K371R) mutant, which does not dissociate from the membrane after translocation. IGF-II stimulation increased diacylglycerol (DAG) levels, the established activator of classical PKC. Interestingly, the polyunsaturated fraction of DAG was increased, indicating involvement of phosphatidyl inositol/phospholipase C (PLC). Pretreating cells with the PLC inhibitor, U73122, attenuated IGF-II-dependent DAG production and PKCβ2 phosphorylation, blocked membrane translocation of the kinase-deficient GFP-PKCβ2 (K371R) mutant, and reduced sphingosine 1-phosphate production, suggesting that PLC/PKCβ2 are upstream regulators of SK1 in the pathway. Taken together, these data provide evidence that activation of PLC and PKCβ2 by the IGF-II/M6P receptor are required for the activation of SK1.
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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.