Characterization of clathrin and Syk interaction upon Shiga toxin binding |
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| Authors: | Sébastien Wälchli Hans-Christian Aasheim Sigrid S. Skånland Bjørn Spilsberg Maria L. Torgersen Ken R. Rosendal Kirsten Sandvig |
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| Affiliation: | 1. Department of Biochemistry, Institute for Cancer Research, Faculty Division: The Norwegian Radium Hospital, Montebello, Oslo, Norway;2. Department of Immunology, Institute for Cancer Research, Faculty Division: The Norwegian Radium Hospital, Montebello, Oslo, Norway;3. Department of Molecular Biosciences, University of Oslo, Oslo, Norway;4. Department of Medical Genetics, Ullevaal University Hospital, Oslo, Norway;5. Centre for Cancer Biomedicine, Faculty Division The Norwegian Radium Hospital, University of Oslo, Norway;1. Department of Environmental Sciences, University of Puerto Rico, Río Piedras Campus, PO Box 70377 San Juan, PR 00936-8377, United States;2. Department of Biology, University of Puerto Rico, Río Piedras Campus, PO Box 23360, San Juan, PR 00931-3360, United States;3. Department of Computer Science, University of Puerto Rico, Río Piedras Campus, PO Box 70377 San Juan, PR 00936-8377, United States;1. Post-Graduate Program in Health Sciences at the State University of Maringá (UEM), Av. Colombo 5790, Bloco 126, CEP 87020-900 Maringá, Paraná, Brazil;2. Department of Basic Health Sciences at the UEM, Av. Colombo 5790, Bloco I-90, CEP 87020-900 Maringá, Paraná, Brazil;3. From the National Physical Laboratory, Teddington, Middlesex TW11 0WL, United Kingdom,;4. the Division of Biomedical Sciences, St. George''s University of London, London SW17 0RE, United Kingdom,;5. the School of Oral and Dental Sciences, University of Bristol, Bristol BS1 2LY, United Kingdom,;6. the Department of Biochemistry, University of Oxford, Parks Road, Oxford OX1 3QU, United Kingdom,;12. the IBM T. J. Watson Research Center, Yorktown Heights, New York 10598;1. Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate School of Medicine, Akita, Japan;2. Department of Chest Surgery, Akita University Graduate School of Medicine, Akita, Japan;3. Department of Biodefense Research, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan;4. Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, Tokyo, Japan;5. Department of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan;6. Life Science Tokyo Advanced Research Center, Hoshi University, Tokyo, Japan;7. Akita University, Akita, Japan |
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| Abstract: | ![]()
Shiga toxin (Stx) is a bacterial toxin that binds to its receptor Gb3 at the plasma membrane. It is taken up by endocytosis and transported retrogradely via the Golgi apparatus to the endoplasmic reticulum. The toxin is then translocated to the cytosol where it exerts its toxic effect. We have previously shown that phosphorylation of clathrin heavy chain (CHC) is an early event following Stx binding to HeLa cells, and that this requires the activity of the tyrosine kinase Syk. Here, we have investigated this event in more detail in the B lymphoid cell line Ramos, which expresses high endogenous levels of both Syk and Gb3. We report that efficient endocytosis of Stx in Ramos cells requires Syk activity and that Syk is recruited to the uptake site of Stx. Furthermore, in response to Stx treatment, CHC and Syk were rapidly phosphorylated in a Src family kinase dependent manner at Y1477 and Y352, respectively. We show that these phosphorylated residues act as binding sites for the direct interaction between Syk and CHC. Interestingly, Syk–CHC complex formation could be induced by both Stx and B cell receptor stimulation. |
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