Abstract
POB1 has been identified as a RalBP1-binding protein and has the Eps15 homology (EH) domain. The EH domain-containing proteins have been suggested to be involved in clathrin-dependent endocytosis. To clarify the function of POB1, we purified a protein which binds to the EH domain of POB1 from bovine brain cytosol and identified it as Epsin, which is known to bind to the EH domain of Eps15. Epsin has three Asn-Pro-Phe (NPF) motifs in the C-terminal region, which are known to form the core sequence for the binding to the EH domain. The EH domain of POB1 interacted directly with the region containing the NPF motifs of Epsin. Expression of Epsin in CHO-IR cells inhibited internalization of insulin although it affected neither insulin-binding nor autophosphorylation activities of the insulin receptor. Taken together with the observations that Epsin is involved in internalization of the receptors for epidermal growth factor and transferrin, these results suggest that Epsin is a binding partner of POB1 and their binding regulates receptor-mediated endocytosis.
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Acknowledgements
We are grateful to Drs Ebina, Nakata, Nakagawa and Hamajima for their providing cells, antibodies, and peptides. We wish to thank the Research Center for Molecular Medicine, Hiroshima University School of Medicine, for the use of their facilities. This work was supported by grants-in-aid for scientific research and for scientific research on priority areas from the Ministry of Education, Science, and Culture, Japan (1997, 1998) and by grants from Yamanouchi Foundation for Research on Metabolic Disorders (1997, 1998), The Naito Foundation (1997), and Kato Memorial Bioscience Foundation (1997).
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Morinaka, K., Koyama, S., Nakashima, S. et al. Epsin binds to the EH domain of POB1 and regulates receptor-mediated endocytosis. Oncogene 18, 5915–5922 (1999). https://doi.org/10.1038/sj.onc.1202974
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DOI: https://doi.org/10.1038/sj.onc.1202974
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