SHP-1: a regulator of neutrophil apoptosis.
The Src homology domain 2 (SH2)-containing tyrosine phosphatase-1 (SHP-1) has been implicated in the regulation of differentiation, proliferation, and activation of hematopoietic cells. In this review, we discuss the potential role of SHP-1 in modulating apoptosis pathways in neutrophils. Low enzymatic SHP-1 was associated with increased neutrophil survival in vitro and SHP-1-deficient mice were reported to develop severe neutrophilic inflammatory responses. In contrast, high expression of this phosphatase was observed in neutropenic patients. Moreover, when neutrophils were exposed to Fas ligand, TNF-alpha, or TRAIL, the anti-apoptotic effects of granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), or IFN-gamma were blocked, most likely by SHP-1-mediated inactivation of anti-apoptotic signaling molecules. In summary, the current available data point to an important role of SHP-1 in the regulation of neutrophil apoptosis.
Yousefi
Shida
S
Department of Pharmacology, University of Bern, Friedbühlstrasse 49, CH-3010 Bern, Switzerland.
Simon
Hans-Uwe
HU
D000818:Animals; D017209:Apoptosis; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D009504:Neutrophils / Q000166:cytology* / Q000201:enzymology* / Q000378:metabolism; D054645:Protein Phosphatase 1; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D050826:Suppressor of Cytokine Signaling Proteins
D016207:Cytokines; D017874:Immediate-Early Proteins; D047908:Intracellular Signaling Peptides and Proteins; D054645:Protein Phosphatase 1; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; D050826:Suppressor of Cytokine Signaling Proteins; C509249:PTPN6 protein, human