ArticleJournal of leukocyte biology2007
Rapid T cell receptor-mediated SHP-1 S591 phosphorylation regulates SHP-1 cellular localization and phosphatase activity.
Article in Journal of leukocyte biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 47 citations in OpenAlex.
- Shp1 phosphatase regulates CXCR2 protein stability and IL8-mediated invasiveness in breast cancer.Cell death & disease · 2026Article
- Consideration of SHP-1 as a Molecular Target for Tumor Therapy.International journal of molecular sciences · 2023Review
- Inhibition of SHP-1 activity by PKC-θ regulates NK cell activation threshold and cytotoxicity.eLife · 2022Article
- Insulin-regulated aminopeptidase contributes to setting the intensity of FcR-mediated inflammation.Frontiers in immunology · 2022Article
- Shp1 in Solid Cancers and Their Therapy.Frontiers in oncology · 2020Review
- Hypoxia Impairs NK Cell Cytotoxicity through SHP-1-Mediated Attenuation of STAT3 and ERK Signaling Pathways.Journal of immunology research · 2020Article
- Loss of Function of DOCK4 in Myelodysplastic Syndromes Stem Cells is Restored by Inhibitors of DOCK4 Signaling Networks.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- 1-Pyrroline-5-carboxylate released by prostate Cancer cell inhibit T cell proliferation and function by targeting SHP1/cytochrome c oxidoreductase/ROS Axis.Journal for immunotherapy of cancer · 2018Article
- Actin retrograde flow controls natural killer cell response by regulating the conformation state of SHP-1.The EMBO journal · 2018Article
- The HNF1α-regulated lncRNA HNF1A-AS1 reverses the malignancy of hepatocellular carcinoma by enhancing the phosphatase activity of SHP-1.Molecular cancer · 2018Article
- Shp1 function in myeloid cells.Journal of leukocyte biology · 2017Review
- Lyn and Fyn function as molecular switches that control immunoreceptors to direct homeostasis or inflammation.Nature communications · 2017Article
- Protein kinase D regulates positive selection of CD4Nature communications · 2016Article
- Constitutive Lck Activity Drives Sensitivity Differences between CD8+ Memory T Cell Subsets.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Cross-Talk between Shp1 and PIPKIγ Controls Leukocyte Recruitment.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Downregulation of inhibitory SRC homology 2 domain-containing phosphatase-1 (SHP-1) leads to recovery of T cell responses in elderly.Cell communication and signaling : CCS · 2014Article
- High NaCl-induced inhibition of PTG contributes to activation of NFAT5 through attenuation of the negative effect of SHP-1.American journal of physiology. Renal physiology · 2013Article
- Protein kinase C-theta (PKCθ) phosphorylates and inhibits the guanine exchange factor, GIV/Girdin.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Regulation of human osteoclast development by dendritic cell-specific transmembrane protein (DC-STAMP).Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2012Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Since the tyrosine phosphatase SHP-1 plays a major role in regulating T cell signaling, we investigated regulation thereof by Ser/Thr phosphorylation. We found that T cell receptor (TCR) stimulation induced fast (<or=1 min) and transient phosphorylation of SHP-1 S591 in both Jurkat and human peripheral blood T-cells (PBT). Phosphorylation of S591 in T-cells could be mediated artificially by a constitutive active PKC-theta construct, but the dose dependence of inhibition by PKC inhibitors indicated that PKCs were not the relevant basophilic kinase in the physiological response. S591 phosphorylation inhibited phosphatase function since a S591D mutant had lower activity than the S591A mutant. Additional evidence that S591 phosphorylation alters SHP-1 function was provided by studies of Jurkat cells stably expressing SHP-1 wild type or mutants. In those cells, S591D mutation reduced the capacity of transfected SHP-1 to inhibit TCR-induced phosphorylation of PLC-gamma1. Interestingly, SHP-1 Y536 phosphorylation (previously shown to augment phosphatase activity) was also induced in PBT by TCR signal but at a much later time compared with S591 ( approximately 30 min). S591 phosphorylation also altered cellular distribution of SHP-1 because: 1) SHP-1 in lipid rafts and a sheared membrane fraction was hypophosphorylated; 2) In stably transfected Jurkat cell lines, S591D mutant protein had reduced presence in both lipid raft and the sheared membrane fraction; 3) S591 phosphorylation prevented nuclear localization of a C-terminal GFP tagged SHP-1 construct. Our studies also shed light on an additional mechanism regulating SHP-1 nuclear localization, namely conformational autoinhibition. These findings highlight elegant regulation of SHP-1 by sequential phosphorylation of serine then tyrosine.
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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.