Gab1 contributes to cytoskeletal reorganization and chemotaxis in response to platelet-derived growth factor.
Kallin, Anders ; Demoulin, Jean-Baptiste ; Nishida, Keigo ; Hirano, Toshio ; Rönnstrand, Lars LU
and Heldin, Carl-Henrik
(2004)
In Journal of Biological Chemistry
279(17).
p.17897-17904
- Abstract
- Gab1 is a scaffolding/docking protein that has been suggested to play a role in signal transduction downstream of certain plasma membrane receptors, including platelet-derived growth factor (PDGF) receptors. We found that PDGF induced a rapid Gab1 phosphorylation, which depended on the recruitment of Grb2, indicating that Grb2 acts as a bridge between Gab1 and the PDGF -receptor. PDGF also enhanced the binding of Gab1 to the phosphatase SHP-2, but not to p85. To further study the role of Gab1 in PDGF signaling, we transfected porcine aortic endothelial cells with a doxycycline-inducible Gab1 construct. Increased Gab1 expression enhanced the recruitment and activation of SHP-2, as well as the phosphorylation of the mitogen-activated protein... (More)
- Gab1 is a scaffolding/docking protein that has been suggested to play a role in signal transduction downstream of certain plasma membrane receptors, including platelet-derived growth factor (PDGF) receptors. We found that PDGF induced a rapid Gab1 phosphorylation, which depended on the recruitment of Grb2, indicating that Grb2 acts as a bridge between Gab1 and the PDGF -receptor. PDGF also enhanced the binding of Gab1 to the phosphatase SHP-2, but not to p85. To further study the role of Gab1 in PDGF signaling, we transfected porcine aortic endothelial cells with a doxycycline-inducible Gab1 construct. Increased Gab1 expression enhanced the recruitment and activation of SHP-2, as well as the phosphorylation of the mitogen-activated protein kinases Erk and p38 by PDGF. Gab1 expression also enhanced the formation of lamellipodia and cellular protrusions. In Gab1-deficient mouse embryonic fibroblasts, the same phenotype was induced by restoring the expression of wild-type Gab1, but not a mutant Gab1 that was unable to associate with SHP-2. These effects of PDGF on the actin cytoskeleton were not altered by the inhibition of p38 or Erk, but could be blocked by a dominant-negative form of Rac (Asn17). Finally, Gab1-deficient fibroblasts showed a decreased chemotactic response toward gradients of PDGF as compared with wild-type cells. In conclusion, Gab1 plays a selective role in the regulation of the mitogen-activated protein kinases Erk and p38 downstream of the PDGF -receptor, and contributes to cytoskeletal reorganization and chemotaxis in response to PDGF. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/121769
- author
- Kallin, Anders
; Demoulin, Jean-Baptiste
; Nishida, Keigo
; Hirano, Toshio
; Rönnstrand, Lars
LU
and Heldin, Carl-Henrik
- publishing date
- 2004
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 279
- issue
- 17
- pages
- 17897 - 17904
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- wos:000220870400123
- scopus:2342418250
- ISSN
- 1083-351X
- DOI
- 10.1074/jbc.M312996200
- 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
- 15cec1b0-ad73-484f-8a32-e03c242f92db (old id 121769)
- date added to LUP
- 2016-04-01 11:49:31
- date last changed
- 2022-01-26 18:46:54
@article{15cec1b0-ad73-484f-8a32-e03c242f92db,
abstract = {{Gab1 is a scaffolding/docking protein that has been suggested to play a role in signal transduction downstream of certain plasma membrane receptors, including platelet-derived growth factor (PDGF) receptors. We found that PDGF induced a rapid Gab1 phosphorylation, which depended on the recruitment of Grb2, indicating that Grb2 acts as a bridge between Gab1 and the PDGF -receptor. PDGF also enhanced the binding of Gab1 to the phosphatase SHP-2, but not to p85. To further study the role of Gab1 in PDGF signaling, we transfected porcine aortic endothelial cells with a doxycycline-inducible Gab1 construct. Increased Gab1 expression enhanced the recruitment and activation of SHP-2, as well as the phosphorylation of the mitogen-activated protein kinases Erk and p38 by PDGF. Gab1 expression also enhanced the formation of lamellipodia and cellular protrusions. In Gab1-deficient mouse embryonic fibroblasts, the same phenotype was induced by restoring the expression of wild-type Gab1, but not a mutant Gab1 that was unable to associate with SHP-2. These effects of PDGF on the actin cytoskeleton were not altered by the inhibition of p38 or Erk, but could be blocked by a dominant-negative form of Rac (Asn17). Finally, Gab1-deficient fibroblasts showed a decreased chemotactic response toward gradients of PDGF as compared with wild-type cells. In conclusion, Gab1 plays a selective role in the regulation of the mitogen-activated protein kinases Erk and p38 downstream of the PDGF -receptor, and contributes to cytoskeletal reorganization and chemotaxis in response to PDGF.}},
author = {{Kallin, Anders and Demoulin, Jean-Baptiste and Nishida, Keigo and Hirano, Toshio and Rönnstrand, Lars and Heldin, Carl-Henrik}},
issn = {{1083-351X}},
language = {{eng}},
number = {{17}},
pages = {{17897--17904}},
publisher = {{American Society for Biochemistry and Molecular Biology}},
series = {{Journal of Biological Chemistry}},
title = {{Gab1 contributes to cytoskeletal reorganization and chemotaxis in response to platelet-derived growth factor.}},
url = {{https://lup.lub.lu.se/search/files/2658375/623985.pdf}},
doi = {{10.1074/jbc.M312996200}},
volume = {{279}},
year = {{2004}},
}