ID 59984
Author
Zhao, Xianglin Graduate School of Natural Science and Technology, Okayama University
Kawano, Shun‐ichiro Graduate School of Natural Science and Technology, Okayama University
Masuda, Junko Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Kaken ID
Murakami, Hiroshi Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University ORCID Kaken ID researchmap
Abstract
Granulocyte colony‐stimulating factor (G‐CSF) stimulation of myeloid cells induced tyrosine‐phosphorylation of cellular proteins. One of the tyrosine‐phosphorylated proteins was found to be a scaffold protein, Grb2‐associated binding protein 2 (Gab2). Another member of Gab family protein, Gab3, was exogenously overexpressed in neutrophil progenitor cells to make the Gab3 protein to compete with the endogenous Gab2 for the G‐CSF‐dependent signaling. In Gab3‐overexpressed cells, the level of tyrosine phosphorylation of endogenous Gab2 by G‐CSF stimulation was markedly downregulated, while the phosphorylation of Gab3 was significantly enhanced. The Gab3‐overexpressed cells continuously proliferated in the medium containing G‐CSF and lost the ability to differentiate to the mature neutrophil, characterized by the lobulated nucleus. The G‐CSF stimulation‐dependent tyrosine phosphorylation of Gab3, the association of SHP2 to Gab3 and the following mitogen‐activated protein kinase (MAPK) activation were prolonged in the Gab3‐overexpressed cells, compared to the parental cells, where the binding of SHP2 to Gab2 protein and thereby the activation of MAPK were not sustained after G‐CSF stimulation. Inhibition of MAPK by pharmaceutical inhibitor restored the Gab3‐overexpressed cells to the ability to differentiate to mature neutrophil. Therefore, G‐CSF‐dependent Gab2 phosphorylation and following its downregulation led the short‐term MAPK activation. The downregulation of MAPK after transient Gab2 phosphorylation was necessary for the consequent neutrophil differentiation induced by G‐CSF stimulation.
Keywords
granulocyte
MAP kinase
negative feedback
phosphorylation
scaffold protein
SHP2
Note
This fulltext is available in May 2021.
Published Date
2020-05-21
Publication Title
Cell Biology International
Publisher
Wiley
ISSN
1065-6995
NCID
AA10882014
Content Type
Journal Article
language
英語
OAI-PMH Set
岡山大学
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Author
PubMed ID
DOI
Web of Science KeyUT
Related Url
isVersionOf https://doi.org/10.1002/cbin.11398