ArticleBlood2013
Identification of a calmodulin-binding domain in Sema4D that regulates its exodomain shedding in platelets.
Article in Blood, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- Glaucocalyxin A inhibits platelet activation and thrombus formation preferentially via GPVI signaling pathway.PloS one · 2013Trial
- Diverse Roles of Semaphorins on T Cell Activation, Differentiation, Migration, and Effector Functions.Cells · 2026Review
- Soluble Sema4D From γδ T Cells Exerts Osteoblast Inhibition via Plexin-B/mTOR Signalling Contributing to Pathogenesis of Bisphosphonate-Related Osteonecrosis of the Jaws.Cell proliferation · 2026Article
- The value of serum Sema4D level in predicting the prognosis of patients with acute ST-segment elevation myocardial infarction and with high thrombus burden.BMC cardiovascular disorders · 2023Article
- The value of serum Sema4D level in reflecting the inflammatory state of acute ST-segment elevation myocardial infarction.Journal of thoracic disease · 2023Article
- Platelet formation and activation are influenced by neuronal guidance proteins.Frontiers in immunology · 2023Review
- Screening and identification of potential biomarkers and therapeutic drugs in melanoma via integrated bioinformatics analysis.Investigational new drugs · 2021Article
- Semaphorin 4D is a potential biomarker in pediatric leukemia and promotes leukemogenesis by activating PI3K/AKT and ERK signaling pathways.Oncology reports · 2021Article
- ACE2 Shedding and the Role in COVID-19.Frontiers in cellular and infection microbiology · 2021Review
- Soluble Sema4D in Plasma of Head and Neck Squamous Cell Carcinoma Patients Is Associated With Underlying Non-Inflamed Tumor Profile.Frontiers in immunology · 2021Article
- Modulation of Immune Responses by Platelet-Derived ADAM10.Frontiers in immunology · 2020Review
- Sema4D expression and secretion are increased by HIF-1α and inhibit osteogenesis in bone metastases of lung cancer.Clinical & experimental metastasis · 2019Article
- Semaphorin4D-PlexinB1 Signaling Attenuates Photoreceptor Outer Segment Phagocytosis by Reducing Rac1 Activity of RPE Cells.Molecular neurobiology · 2018Article
- Regulation of A disintegrin and metalloproteinase (ADAM) family sheddases ADAM10 and ADAM17: The emerging role of tetraspanins and rhomboids.Platelets · 2017Review
- Transmembrane semaphorins: Multimodal signaling cues in development and cancer.Cell adhesion & migration · 2016Review
- Semaphorin 4D Contributes to Rheumatoid Arthritis by Inducing Inflammatory Cytokine Production: Pathogenic and Therapeutic Implications.Arthritis & rheumatology (Hoboken, N.J.) · 2015Article
- Modulation of platelet activation and thrombus formation using a pan-PI3K inhibitor S14161.PloS one · 2014Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Semaphorin 4D (Sema4D) is a transmembrane protein that supports contact-dependent amplification of platelet activation by collagen before being gradually cleaved by the metalloprotease ADAM17, as we have previously shown. Cleavage releases a soluble 120-kDa exodomain fragment for which receptors exist on platelets and endothelial cells. Here we have examined the mechanism that regulates Sema4D exodomain cleavage. The results show that the membrane-proximal cytoplasmic domain of Sema4D contains a binding site for calmodulin within the polybasic region Arg762-Lys779. Coprecipitation studies show that Sema4D and calmodulin are associated in resting platelets, forming a complex that dissociates upon platelet activation by the agonists that trigger Sema4D cleavage. Inhibiting calmodulin with W7 or introducing a membrane-permeable peptide corresponding to the calmodulin-binding site is sufficient to trigger the dissociation of Sema4D from calmodulin and initiate cleavage. Conversely, deletion of the calmodulin-binding site causes constitutive shedding of Sema4D. These results show that (1) Sema4D is a calmodulin-binding protein with a site of interaction in its membrane-proximal cytoplasmic domain, (2) platelet agonists cause dissociation of the calmodulin-Sema4D complex, and (3) dissociation of the complex is sufficient to trigger ADAM17-dependent cleavage of Sema4D, releasing a bioactive fragment.
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Registered trials
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