Cell Signal 2008,
PMID: 18644434
Wang, Lin; Xue, Jia; Zadorozny, Eva V; Robinson, Lisa J
Granulocyte colony-stimulating factor (G-CSF), the major cytokine regulator of neutrophilic granulopoiesis, stimulates both the proliferation and differentiation of myeloid precursors. A variety of signaling proteins have been identified as mediators of G-CSF signaling, but understanding of their specific interactions and organization into signaling pathways for particular cellular effects is incomplete. The present study examined the role of the scaffolding protein Grb2-associated binding protein-2 (Gab2) in G-CSF signaling. We found that a chemical inhibitor of Janus kinases inhibited G-CSF-stimulated Gab2 phosphorylation. Transfection with Jak2 antisense and dominant negative constructs also inhibited Gab2 phosphorylation in response to G-CSF. In addition, G-CSF enhanced the association of Jak2 with Gab2. In vitro, activated Jak2 directly phosphorylated specific Gab2 tyrosine residues. Mutagenesis studies revealed that Gab2 tyrosine 643 (Y643) was a major target of Jak2 in vitro, and a key residue for Jak2-dependent phosphorylation in intact cells. Mutation of Gab2 Y643 inhibited G-CSF-stimulated Erk1/2 activation and Shp2 binding to Gab2. Loss of Y643 also inhibited Gab2-mediated G-CSF-stimulated cell proliferation. Together, these results identify a novel signaling pathway involving Jak2-dependent Gab2 phosphorylation leading to Erk1/2 activation and cell proliferation in response to G-CSF.
Document information provided by NCBI PubMed
Text Mining Data
Gab2 → G-CSF: "
G-CSF stimulates Jak2 dependent
Gab2 phosphorylation leading to Erk1/2 activation and cell proliferation
"
Gab2 → Jak2: "
G-CSF stimulates Jak2 dependent Gab2 phosphorylation leading to Erk1/2 activation and cell proliferation
"
G-CSF ⊣ Grb2 associated binding protein-2 (Gab2): "
The present study examined the role of the scaffolding protein Grb2 associated binding protein-2 (Gab2) in G-CSF signaling
"
Gab2 → G-CSF: "
We found that a chemical inhibitor of Janus kinases inhibited G-CSF stimulated Gab2 phosphorylation
"
Gab2 → G-CSF: "
Transfection with Jak2 antisense and dominant negative constructs also inhibited Gab2 phosphorylation in response to G-CSF
"
Gab2 → G-CSF: "
In addition, G-CSF enhanced the association of Jak2 with Gab2
"
Jak2 → G-CSF: "
In addition, G-CSF enhanced the association of Jak2 with Gab2
"
Gab2 → G-CSF: "
Mutation of Gab2 Y643 inhibited G-CSF stimulated Erk1/2 activation and Shp2 binding to Gab2
"
Erk1/2 → G-CSF: "
Mutation of Gab2 Y643 inhibited G-CSF stimulated Erk1/2 activation and Shp2 binding to Gab2
"
Erk1/2 → G-CSF: "
Mutation of Gab2 Y643 inhibited G-CSF stimulated Erk1/2 activation and Shp2 binding to Gab2
"
Shp2 → G-CSF: "
Mutation of Gab2 Y643 inhibited G-CSF stimulated Erk1/2 activation and Shp2 binding to Gab2
"
Gab2 → Jak2: "
Together, these results identify a novel signaling pathway involving Jak2 dependent Gab2 phosphorylation leading to Erk1/2 activation and cell proliferation in response to G-CSF
"
Manually curated Databases
No curated data.