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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)
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published
subject
keywords
Amino Acid Sequence Animals Aorta Clone Cells *Endocytosis Endothelium, Vascular/*metabolism Humans Iodine Radioisotopes Kinetics Molecular Sequence Data Mutagenesis, IGF Type 2/chemistry Receptors, Site-Directed Platelet-Derived Growth Factor/*metabolism Receptor, Platelet-Derived Growth Factor/biosynthesis/chemistry/*metabolism Recombinant Proteins/metabolism Sequence Homology, Amino Acid Swine Transfection *Tyrosine
in
Journal of Biological Chemistry
volume
269
issue
7
pages
4917 - 4921
publisher
ASBMB
ISSN
1083-351X
language
English
LU publication?
no
id
d7f11822-4f55-4366-b303-200c513b1e66 (old id 1783992)
alternative location
http://www.jbc.org/content/269/7/4917.abstract
date added to LUP
2011-02-07 15:40:19
date last changed
2016-06-29 09:16:48
@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},
  keyword      = {Amino Acid Sequence
Animals
Aorta
Clone Cells
*Endocytosis
Endothelium,Vascular/*metabolism
Humans
Iodine Radioisotopes
Kinetics
Molecular Sequence Data
Mutagenesis,IGF Type 2/chemistry
Receptors,Site-Directed
Platelet-Derived Growth Factor/*metabolism
Receptor,Platelet-Derived Growth
Factor/biosynthesis/chemistry/*metabolism
Recombinant Proteins/metabolism
Sequence Homology,Amino Acid
Swine
Transfection
*Tyrosine},
  language     = {eng},
  number       = {7},
  pages        = {4917--4921},
  publisher    = {ASBMB},
  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},
  volume       = {269},
  year         = {1994},
}