ArticleThe Journal of biological chemistry2008
Neph1, a component of the kidney slit diaphragm, is tyrosine-phosphorylated by the Src family tyrosine kinase and modulates intracellular signaling by binding to Grb2.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 82 citations in OpenAlex.
- Structural and functional insights of the podocyte slit diaphragm complex.Tissue barriers · 2026Review
- The Life of a Kidney Podocyte.Acta physiologica (Oxford, England) · 2025Review
- SIRPα modulates the podocyte cytoskeleton through influencing the phosphorylation of FAK at tyrosine residue 597.Acta biochimica et biophysica Sinica · 2024Article
- Glycosphingolipid GM3 prevents albuminuria and podocytopathy induced by anti-nephrin antibody.Scientific reports · 2022Article
- New Insights into the Treatment of Glomerular Diseases: When Mechanisms Become Vivid.International journal of molecular sciences · 2022Review
- Renal cell markers: lighthouses for managing renal diseases.American journal of physiology. Renal physiology · 2021Article
- Molecular and structural basis of olfactory sensory neuron axon coalescence by Kirrel receptors.Cell reports · 2021Article
- Evolutionary conservation of intrinsically unstructured regions in slit-diaphragm proteins.PloS one · 2021Article
- High-speed single-molecule imaging reveals signal transduction by induced transbilayer raft phases.The Journal of cell biology · 2020Article
- SHROOM3, the gene associated with chronic kidney disease, affects the podocyte structure.Scientific reports · 2020Article
- Review
- New insight into podocyte slit diaphragm, a therapeutic target of proteinuria.Clinical and experimental nephrology · 2020Review
- Mutations in KIRREL1, a slit diaphragm component, cause steroid-resistant nephrotic syndrome.Kidney international · 2019Article
- A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes.Cell reports · 2018Article
- Acute Kidney Injury and Progression of Diabetic Kidney Disease.Advances in chronic kidney disease · 2018Review
- Proteinuric Kidney Diseases: A Podocyte's Slit Diaphragm and Cytoskeleton Approach.Frontiers in medicine · 2018Review
- Candidate genes in gastric cancer identified by constructing a weighted gene co-expression network.PeerJ · 2018Article
- Identification of novel therapeutic target genes and pathway in pancreatic cancer by integrative analysis.Medicine · 2017Article
- Targeting Neph1 and ZO-1 protein-protein interaction in podocytes prevents podocyte injury and preserves glomerular filtration function.Scientific reports · 2017Article
- Glomerulosclerosis Induced by Deficiency of Membrane-Associated Guanylate Kinase Inverted 2 in Kidney Podocytes.Journal of the American Society of Nephrology : JASN · 2017Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There are several lines of evidence that the podocyte slit diaphragm (SD), which serves as a structural framework for the filtration barrier in kidney glomerulus, also plays an essential role as a signaling platform. Several SD components including nephrin and TRPC6 are known to be phosphorylated by a Src family tyrosine kinase (SFK), Fyn. Here we have characterized Neph1, another SD component, as a novel substrate of SFK. Fyn interacts with and phosphorylates the cytoplasmic domain of Neph1 in vitro and in intact cells. Peptide mass fingerprinting and site-directed mutagenesis identified several tyrosine phosphorylation sites. In pull-down assays using rat glomerular lysates, Neph1 but not nephrin specifically binds to adaptor protein Grb2 and tyrosine kinase Csk in a phosphorylation-dependent manner. Both tyrosine 637 and 638 of Neph1 are crucial for Neph1-Grb2 binding. Phosphorylation of tyrosine 637 is significantly up-regulated in in vivo models of podocyte injury. Furthermore, Neph1 attenuates ERK activation elicited by Fyn, and this inhibitory effect requires the intact binding motif for the Grb2 SH2 domain. Our results shown here demonstrate that Neph1 is a novel in vivo substrate of SFK and suggest that Neph1 modulates ERK signaling through phosphorylation-dependent interaction with Grb2. Thus, SFK orchestrates a wide spectrum of protein-protein interactions and intracellular signaling networks at SD through tyrosine phosphorylation.
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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.