| Autor: |
Gaits, Frédérique, Li, Ruo Ya, Bigay, Joëlle, Ragab, Ashraf, Ragab-Thomas, Jeannie M.F., Chap, Hugues |
| Zdroj: |
Journal of Biological Chemistry; August 1996, Vol. 271 Issue: 33 p20151-20155, 5p |
| Abstrakt: |
SH-PTP1 is a protein-tyrosine phosphatase preferentially expressed in hematopoietic cells and bearing two SH2 (rchomology-2) domains. In the human megakaryocytic cell line Dami, lysophosphatidic acid (LPA) promoted a rapid increase in SH-PTP1 phosphorylation on both serine and tyrosine residues. Only tyrosine phosphorylation was significantly inhibited by pertussis toxin and by the protein kinase C inhibitor GF109203X. Moreover, SH-PTP1 was phosphorylated upon challenge with other agonists acting via G-protein-coupled receptors such as α-thrombin, epinephrine, and ADP, whereas the closely related protein-tyrosine phosphatase SH-PTP2 failed to share such a regulation in Dami cells. We developed an in vitroassay that reproduced LPA-dependent phosphorylation of SH-PTP1 in a cell-free system. The fusion protein glutathione S-transferase-β-adrenergic receptor kinase 1-(495-689) or the transducin subunit Gαt-GDP, which act as specific antagonists of Gβγ, inhibited SH-PTP1 phosphorylation. Moreover, purified transducin Gβγ subunits mimicked the effect of LPA. Finally, stable expression of β-adrenergic receptor kinase 1-(495-689) in Dami cells resulted in the inhibition of SH-PTP1 phosphorylation evoked by LPA. Our data thus identify SH-PTP1 as a specific target of protein kinases linked to G-protein-coupled receptors via Gβγ subunits. |
| Databáze: |
Supplemental Index |
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