{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:08:20Z","timestamp":1791331700565,"version":"4.3.1"},"reference-count":46,"publisher":"The Company of Biologists","issue":"24","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,12,15]]},"abstract":"<jats:p>Mutations of the critical and rate-limiting melanogenic enzyme tyrosinase (Tyr) result in hypopigmentation of the hair, skin and eyes. Two other related enzymes, Tyrp1 and Dct, catalyze distinct post-Tyr reactions in melanin biosynthesis. Tyr, Tyrp1 and Dct have been proposed to interact with and stabilize each other in multi-enzyme complexes, and in vitro, Tyr activity is more stable in the presence of Tyrp1 and\/or Dct. We recently reported that Tyr is degraded more quickly in mutant Tyrp1 mouse melanocytes than in wild-type Tyrp1 melanocytes, and that decreased stability of Tyr can be partly rescued by infection with wild-type Tyrp1. Although interactions between Tyr and Tyrp1 have been demonstrated in vitro, there is no direct evidence for Tyr interaction with Tyrp1 in vivo. In this study, we use in vivo chemical crosslinking to stabilize the association of Tyr with other cellular proteins. Western blot analysis revealed that Tyrp1, but not Dct, associates with Tyr in murine melanocytes in vivo, and more specifically, in melanosomes. Two-dimensional SDS-PAGE analysis detected heterodimeric species of Tyr and Tyrp1. Taken together, these data demonstrate that Tyrp1 interacts directly with Tyr in vivo, which may regulate the stability and trafficking of melanogenic enzymes and thus pigment synthesis.<\/jats:p>","DOI":"10.1242\/jcs.017913","type":"journal-article","created":{"date-parts":[[2007,11,28]],"date-time":"2007-11-28T01:26:23Z","timestamp":1196213183000},"page":"4261-4268","source":"Crossref","is-referenced-by-count":75,"title":["Direct interaction of tyrosinase with Tyrp1 to form heterodimeric complexes in vivo"],"prefix":"10.1242","volume":"120","author":[{"given":"Takeshi","family":"Kobayashi","sequence":"first","affiliation":[{"name":"Department of Physiology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent J.","family":"Hearing","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042520050095500_REF1","doi-asserted-by":"crossref","unstructured":"Bennett, D. C. (1991). Colour genes, oncogenes and melanocyte differentiation. J. Cell Sci.98, 135-139.","DOI":"10.1242\/jcs.98.2.135"},{"key":"2021042520050095500_REF2","doi-asserted-by":"crossref","unstructured":"Bennett, D. C., Cooper, P. J. and Hart, I. R. (1987). A line of non-tumorigenic mouse melanocytes, syngeneic with the B16 melanoma and requiring a tumor promoter for growth. Int. J. Cancer39, 414-418.","DOI":"10.1002\/ijc.2910390324"},{"key":"2021042520050095500_REF3","doi-asserted-by":"crossref","unstructured":"Bennett, D. C., Cooper, P. J., Dexter, T. H., Devlin, L. M., Heasman, J. and Nester, B. (1989). Cloned mouse melanocyte lines carrying germline mutations albino and brown: complementation in culture. Development105, 379-385.","DOI":"10.1242\/dev.105.2.379"},{"key":"2021042520050095500_REF4","unstructured":"Boissy, R. E., Zhao, H., Oetting, W. S., Austin, L. M., Wildenberg, S. C., Boissy, Y. L., Zhao, Y., Sturm, R. A., Hearing, V. J., King, R. A. et al. (1996). 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Tyrosinase maturation through the mammalian secretory pathway: bringing color to life. Pigment Cell Res.19, 3-18.","DOI":"10.1111\/j.1600-0749.2005.00288.x"},{"key":"2021042520050095500_REF43","unstructured":"Winder, A. J., Kobayashi, T., Tsukamoto, K., Urabe, K., Aroca, P., Kameyama, K. and Hearing, V. J. (1994). The tyrosinase gene family: Interactions of melanogenic proteins to regulate melanogenesis. Cell. Mol. Biol. Res.40, 613-626."},{"key":"2021042520050095500_REF44","doi-asserted-by":"crossref","unstructured":"Wu, H. and Park, H. Y. (2003). Protein kinase C-beta-mediated complex formation between tyrosinase and TRP-1. Biochem. Biophys. Res. Commun.311, 948-953.","DOI":"10.1016\/j.bbrc.2003.10.092"},{"key":"2021042520050095500_REF45","doi-asserted-by":"crossref","unstructured":"Yasumoto, K., Watabe, H., Valencia, J. C., Kushimoto, T., Kobayashi, T., Appella, E. and Hearing, V. J. (2004). 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