A tyrosine residue in the juxtamembrane segment of the platelet-derived growth factor beta-receptor is critical for ligand-mediated endocytosis
Mori, Seijiro ; Rönnstrand, Lars LU
; Claesson-Welsh, Lena
and Heldin, Carl-Henrik
(1994)
In Journal of Biological Chemistry
269(7).
p.4917-4921
- Abstract
- The importance of tyrosine residues in ligand-mediated endocytosis of the platelet-derived growth factor beta-receptor was analyzed using a series of tyrosine residue-mutated beta-receptors, which together cover all of the tyrosine residues in the juxtamembrane segment, the kinase insert, and the carboxyl-terminal tail; also certain of the tyrosine residues within the first and second parts of the kinase domain were examined. Of all of these tyrosine residues, only Tyr-579 seemed to be important for internalization, since mutation of this residue resulted in substantial reduction in the rate of ligand-induced receptor internalization (approximately 60% of the wild-type level). Replacement of Tyr-579 by either an aromatic (Phe) or a... (More)
- The importance of tyrosine residues in ligand-mediated endocytosis of the platelet-derived growth factor beta-receptor was analyzed using a series of tyrosine residue-mutated beta-receptors, which together cover all of the tyrosine residues in the juxtamembrane segment, the kinase insert, and the carboxyl-terminal tail; also certain of the tyrosine residues within the first and second parts of the kinase domain were examined. Of all of these tyrosine residues, only Tyr-579 seemed to be important for internalization, since mutation of this residue resulted in substantial reduction in the rate of ligand-induced receptor internalization (approximately 60% of the wild-type level). Replacement of Tyr-579 by either an aromatic (Phe) or a nonaromatic (Asp) residue reduced the efficiency of the mutant receptors in internalization to the same extent, suggesting that the role of Tyr-579 in the beta-receptor is different from that of the previously described tyrosine-based internalization motifs, which were first determined for the low density lipoprotein receptor. Tyr-579 has been found to be an autophosphorylation site in the beta-receptor. Moreover, the internalization rate of a kinase negative receptor mutant was not altered by the additional mutation of Tyr-579. Thus, it is likely that phosphorylation of Tyr-579 is important for ligand-induced internalization of the beta-receptor. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1783992
- author
- Mori, Seijiro
; Rönnstrand, Lars
LU
; Claesson-Welsh, Lena
and Heldin, Carl-Henrik
- publishing date
- 1994
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Amino Acid SequenceAnimalsAortaClone Cells*EndocytosisEndothelium, Vascular/*metabolismHumansIodine RadioisotopesKineticsMolecular Sequence DataMutagenesis, IGF Type 2/chemistryReceptors, Site-DirectedPlatelet-Derived Growth Factor/*metabolismReceptor, Platelet-Derived GrowthFactor/biosynthesis/chemistry/*metabolismRecombinant Proteins/metabolismSequence Homology, Amino AcidSwineTransfection*Tyrosine
- in
- Journal of Biological Chemistry
- volume
- 269
- issue
- 7
- pages
- 4917 - 4921
- publisher
- American Society for Biochemistry and Molecular Biology
- ISSN
- 1083-351X
- language
- English
- LU publication?
- no
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Experimental Clinical Chemistry (013016010)
- id
- d7f11822-4f55-4366-b303-200c513b1e66 (old id 1783992)
- alternative location
- http://www.jbc.org/content/269/7/4917.abstract
- date added to LUP
- 2016-04-04 08:54:56
- date last changed
- 2021-01-04 15:49:46
@article{d7f11822-4f55-4366-b303-200c513b1e66,
abstract = {{The importance of tyrosine residues in ligand-mediated endocytosis of the platelet-derived growth factor beta-receptor was analyzed using a series of tyrosine residue-mutated beta-receptors, which together cover all of the tyrosine residues in the juxtamembrane segment, the kinase insert, and the carboxyl-terminal tail; also certain of the tyrosine residues within the first and second parts of the kinase domain were examined. Of all of these tyrosine residues, only Tyr-579 seemed to be important for internalization, since mutation of this residue resulted in substantial reduction in the rate of ligand-induced receptor internalization (approximately 60% of the wild-type level). Replacement of Tyr-579 by either an aromatic (Phe) or a nonaromatic (Asp) residue reduced the efficiency of the mutant receptors in internalization to the same extent, suggesting that the role of Tyr-579 in the beta-receptor is different from that of the previously described tyrosine-based internalization motifs, which were first determined for the low density lipoprotein receptor. Tyr-579 has been found to be an autophosphorylation site in the beta-receptor. Moreover, the internalization rate of a kinase negative receptor mutant was not altered by the additional mutation of Tyr-579. Thus, it is likely that phosphorylation of Tyr-579 is important for ligand-induced internalization of the beta-receptor.}},
author = {{Mori, Seijiro and Rönnstrand, Lars and Claesson-Welsh, Lena and Heldin, Carl-Henrik}},
issn = {{1083-351X}},
keywords = {{Amino Acid SequenceAnimalsAortaClone Cells*EndocytosisEndothelium; Vascular/*metabolismHumansIodine RadioisotopesKineticsMolecular Sequence DataMutagenesis; IGF Type 2/chemistryReceptors; Site-DirectedPlatelet-Derived Growth Factor/*metabolismReceptor; Platelet-Derived GrowthFactor/biosynthesis/chemistry/*metabolismRecombinant Proteins/metabolismSequence Homology; Amino AcidSwineTransfection*Tyrosine}},
language = {{eng}},
number = {{7}},
pages = {{4917--4921}},
publisher = {{American Society for Biochemistry and Molecular Biology}},
series = {{Journal of Biological Chemistry}},
title = {{A tyrosine residue in the juxtamembrane segment of the platelet-derived growth factor beta-receptor is critical for ligand-mediated endocytosis}},
url = {{http://www.jbc.org/content/269/7/4917.abstract}},
volume = {{269}},
year = {{1994}},
}