Structural determinants in the platelet-derived growth factor alpha-receptor implicated in modulation of chemotaxis
(1996) In Journal of Biological Chemistry 271(9). p.5101-5111- Abstract
- Activation of the platelet-derived growth factor (PDGF) beta-receptor leads to cell growth and chemotaxis. The PDGF alpha-receptor also mediates a mitogenic signal, but fails to induce cell migration in certain cell types. To examine this difference in signal transduction, a series of point-mutated PDGF alpha-receptors were analyzed. Porcine aortic endothelial cells expressing mutant PDGF alpha-receptors, in which tyrosine residues 768, 993, or 1018 were changed to phenylalanine residues migrated toward PDGF, whereas wild-type alpha-receptors and mutant alpha-receptors changed at tyrosine residues 720, 944, or 988 failed to migrate. All mutant receptors were mitogenically active and their capacity to activate phosphatidylinositol 3'-kinase... (More)
- Activation of the platelet-derived growth factor (PDGF) beta-receptor leads to cell growth and chemotaxis. The PDGF alpha-receptor also mediates a mitogenic signal, but fails to induce cell migration in certain cell types. To examine this difference in signal transduction, a series of point-mutated PDGF alpha-receptors were analyzed. Porcine aortic endothelial cells expressing mutant PDGF alpha-receptors, in which tyrosine residues 768, 993, or 1018 were changed to phenylalanine residues migrated toward PDGF, whereas wild-type alpha-receptors and mutant alpha-receptors changed at tyrosine residues 720, 944, or 988 failed to migrate. All mutant receptors were mitogenically active and their capacity to activate phosphatidylinositol 3'-kinase and phospholipase C-gamma was not different from that of the wild-type receptor. Tyr-768 was found to be phosphorylated in PDGF-stimulated cells; in the Y768F mutant, there was a considerable increase in phosphorylation of Ser-767. Tyr-993 was not phosphorylated, but mutation of this tyrosine residue to a phenylalanine residue resulted in increased efficiency of phosphorylation on Tyr-988. Tyr-1018 is known to be an autophosphorylation site. Phosphorylated Tyr-768 and Tyr-1018 may bind signal transduction molecules involved in negative modulation of the chemotactic signaling capacity, whereas phosphorylated Tyr-988 may mediate increased chemotaxis. Thus our data indicate that the PDGF alpha-receptor has an intrinsic ability to transduce a chemotactic signal, and that this signal is counteracted by overriding negative signals. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1783946
- author
- Yokote, Koutaro ; Mori, Seijiro ; Siegbahn, Agneta ; Rönnstrand, Lars LU ; Wernstedt, Christer ; Heldin, Carl-Henrik and Claesson-Welsh, Lena
- publishing date
- 1996
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Amino Acid Sequence Animals Aorta Base Sequence Cell Line *Chemotaxis/drug effects Endothelium, Vascular/*physiology Enzyme Activation Humans Inositol Phosphates/metabolism Isoenzymes/metabolism Kinetics Molecular Sequence Data Mutagenesis, Site-Directed Oligodeoxyribonucleotides Peptide Fragments/chemistry/isolation & purification Phenylalanine Phosphatidylinositol 3-Kinases Phosphopeptides/chemistry/isolation & purification Phosphotransferases (Alcohol Group Acceptor)/metabolism Platelet-Derived Growth Factor/*pharmacology *Point Mutation Receptor, Platelet-Derived Growth Factor alpha Receptors, Platelet-Derived Growth Factor/biosynthesis/*chemistry/*physiology Recombinant Proteins/biosynthesis/chemistry/metabolism Signal Transduction Swine Transfection Type C Phospholipases/metabolism Tyrosine
- in
- Journal of Biological Chemistry
- volume
- 271
- issue
- 9
- pages
- 5101 - 5111
- 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
- 4e749139-ad7c-4a1f-94ac-9ea26d53ed2b (old id 1783946)
- date added to LUP
- 2016-04-04 08:03:56
- date last changed
- 2019-05-22 02:18:32
@article{4e749139-ad7c-4a1f-94ac-9ea26d53ed2b, abstract = {{Activation of the platelet-derived growth factor (PDGF) beta-receptor leads to cell growth and chemotaxis. The PDGF alpha-receptor also mediates a mitogenic signal, but fails to induce cell migration in certain cell types. To examine this difference in signal transduction, a series of point-mutated PDGF alpha-receptors were analyzed. Porcine aortic endothelial cells expressing mutant PDGF alpha-receptors, in which tyrosine residues 768, 993, or 1018 were changed to phenylalanine residues migrated toward PDGF, whereas wild-type alpha-receptors and mutant alpha-receptors changed at tyrosine residues 720, 944, or 988 failed to migrate. All mutant receptors were mitogenically active and their capacity to activate phosphatidylinositol 3'-kinase and phospholipase C-gamma was not different from that of the wild-type receptor. Tyr-768 was found to be phosphorylated in PDGF-stimulated cells; in the Y768F mutant, there was a considerable increase in phosphorylation of Ser-767. Tyr-993 was not phosphorylated, but mutation of this tyrosine residue to a phenylalanine residue resulted in increased efficiency of phosphorylation on Tyr-988. Tyr-1018 is known to be an autophosphorylation site. Phosphorylated Tyr-768 and Tyr-1018 may bind signal transduction molecules involved in negative modulation of the chemotactic signaling capacity, whereas phosphorylated Tyr-988 may mediate increased chemotaxis. Thus our data indicate that the PDGF alpha-receptor has an intrinsic ability to transduce a chemotactic signal, and that this signal is counteracted by overriding negative signals.}}, author = {{Yokote, Koutaro and Mori, Seijiro and Siegbahn, Agneta and Rönnstrand, Lars and Wernstedt, Christer and Heldin, Carl-Henrik and Claesson-Welsh, Lena}}, issn = {{1083-351X}}, keywords = {{Amino Acid Sequence Animals Aorta Base Sequence Cell Line *Chemotaxis/drug effects Endothelium; Vascular/*physiology Enzyme Activation Humans Inositol Phosphates/metabolism Isoenzymes/metabolism Kinetics Molecular Sequence Data Mutagenesis; Site-Directed Oligodeoxyribonucleotides Peptide Fragments/chemistry/isolation & purification Phenylalanine Phosphatidylinositol 3-Kinases Phosphopeptides/chemistry/isolation & purification Phosphotransferases (Alcohol Group Acceptor)/metabolism Platelet-Derived Growth Factor/*pharmacology *Point Mutation Receptor; Platelet-Derived Growth Factor alpha Receptors; Platelet-Derived Growth Factor/biosynthesis/*chemistry/*physiology Recombinant Proteins/biosynthesis/chemistry/metabolism Signal Transduction Swine Transfection Type C Phospholipases/metabolism Tyrosine}}, language = {{eng}}, number = {{9}}, pages = {{5101--5111}}, publisher = {{American Society for Biochemistry and Molecular Biology}}, series = {{Journal of Biological Chemistry}}, title = {{Structural determinants in the platelet-derived growth factor alpha-receptor implicated in modulation of chemotaxis}}, volume = {{271}}, year = {{1996}}, }