Show simple item record

dc.contributor.authorGirones, Nuria
dc.contributor.authorAlvarez, Elvira
dc.contributor.authorSeth, Alpna
dc.contributor.authorLin, I-Mei
dc.contributor.authorLatour, Debra A.
dc.contributor.authorDavis, Roger J.
dc.date2022-08-11T08:08:57.000
dc.date.accessioned2022-08-23T16:13:54Z
dc.date.available2022-08-23T16:13:54Z
dc.date.issued1991-10-05
dc.date.submitted2008-09-11
dc.identifier.citation<p>J Biol Chem. 1991 Oct 5;266(28):19006-12.</p>
dc.identifier.issn0021-9258 (Print)
dc.identifier.pmid1918016
dc.identifier.urihttp://hdl.handle.net/20.500.14038/33734
dc.description.abstractIt has been reported that the sequence Tyr20-X-Arg-Phe23 present within the cytoplasmic tail of the transferrin receptor may represent a tyrosine internalization signal (Collawn, J.F., Stangel, M., Kuhn, L.A., Esekogwu, V., Jing, S., Trowbridge, I.S., and Tainer, J. A. (1990) Cell 63, 1061-1072). However, as Tyr20 is not conserved between species (Alvarez, E., Girones, N., and Davis, R. J. (1990) Biochem. J. 267, 31-35), the functional role of the putative tyrosine internalization signal is not clear. To address this question, we constructed a series of 32 deletions and point mutations within the cytoplasmic tail of the human transferrin receptor. The effect of these mutations on the apparent first order rate constant for receptor endocytosis was examined. It was found that the region of the cytoplasmic tail that is proximal to the transmembrane domain (residues 28-58) is dispensable for rapid endocytosis. In contrast, the distal region of the cytoplasmic tail (residues 1-27) was found to be both necessary and sufficient for the rapid internalization of the transferrin receptor. The region identified includes Tyr20-X-Arg-Phe23, but is significantly larger than this tetrapeptide. It is therefore likely that structural information in addition to the proposed tyrosine internalization signal is required for endocytosis. To test this hypothesis, we investigated whether a heterologous tyrosine internalization signal (from the low density lipoprotein receptor) could function to cause the rapid endocytosis of the transferrin receptor. It was observed that this heterologous tyrosine internalization signal did not allow rapid endocytosis. We conclude that the putative tyrosine internalization signal (Tyr20-Thr-Arg-Phe23) is not sufficient to determine rapid endocytosis of the transferrin receptor. The data reported here indicate that the transferrin receptor internalization signal is formed by a larger cytoplasmic tail structure located at the amino terminus of the receptor.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1918016&dopt=Abstract ">Link to article in PubMed</a></p>
dc.relation.urlhttp://www.jbc.org/content/266/28/19006.short
dc.subjectAmino Acid Sequence; Animals; Cell Line; Cricetinae; Cytoplasm; *Endocytosis; Humans; Kinetics; Molecular Sequence Data; Mutation; Receptors, LDL; Receptors, Transferrin; Tyrosine
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleMutational analysis of the cytoplasmic tail of the human transferrin receptor. Identification of a sub-domain that is required for rapid endocytosis
dc.typeJournal Article
dc.source.journaltitleThe Journal of biological chemistry
dc.source.volume266
dc.source.issue28
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_sp/397
dc.identifier.contextkey627234
html.description.abstract<p>It has been reported that the sequence Tyr20-X-Arg-Phe23 present within the cytoplasmic tail of the transferrin receptor may represent a tyrosine internalization signal (Collawn, J.F., Stangel, M., Kuhn, L.A., Esekogwu, V., Jing, S., Trowbridge, I.S., and Tainer, J. A. (1990) Cell 63, 1061-1072). However, as Tyr20 is not conserved between species (Alvarez, E., Girones, N., and Davis, R. J. (1990) Biochem. J. 267, 31-35), the functional role of the putative tyrosine internalization signal is not clear. To address this question, we constructed a series of 32 deletions and point mutations within the cytoplasmic tail of the human transferrin receptor. The effect of these mutations on the apparent first order rate constant for receptor endocytosis was examined. It was found that the region of the cytoplasmic tail that is proximal to the transmembrane domain (residues 28-58) is dispensable for rapid endocytosis. In contrast, the distal region of the cytoplasmic tail (residues 1-27) was found to be both necessary and sufficient for the rapid internalization of the transferrin receptor. The region identified includes Tyr20-X-Arg-Phe23, but is significantly larger than this tetrapeptide. It is therefore likely that structural information in addition to the proposed tyrosine internalization signal is required for endocytosis. To test this hypothesis, we investigated whether a heterologous tyrosine internalization signal (from the low density lipoprotein receptor) could function to cause the rapid endocytosis of the transferrin receptor. It was observed that this heterologous tyrosine internalization signal did not allow rapid endocytosis. We conclude that the putative tyrosine internalization signal (Tyr20-Thr-Arg-Phe23) is not sufficient to determine rapid endocytosis of the transferrin receptor. The data reported here indicate that the transferrin receptor internalization signal is formed by a larger cytoplasmic tail structure located at the amino terminus of the receptor.</p>
dc.identifier.submissionpathgsbs_sp/397
dc.contributor.departmentHoward Hughes Medical Institute, Program in Molecular Medicine
dc.contributor.departmentGraduate School of Biomedical Sciences
dc.source.pages19006-12


This item appears in the following Collection(s)

Show simple item record