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Blood, 15 January 2002, Vol. 99, No. 2, pp. 694-697
BRIEF REPORT
PTEN controls immunoreceptor (immunoreceptor tyrosine-based
activation motif) signaling and the activation of Rac
Jong Suk Kim,
Xiaodong Peng,
Pradip K. De,
Robert L. Geahlen, and
Donald
L. Durden
From the Departments of Pediatrics, Biochemistry, and
Molecular Biology, Herman B. Wells Center for Pediatric Research,
Indiana University School of Medicine, Indianapolis; and the Department
of Medicinal Chemistry and Molecular Pharmacology, Purdue University,
West Lafayette, IN.
Fc receptor-mediated phagocytosis is a model for the
study of immunoreceptor (immunoreceptor tyrosine-based activation motif [ITAM]) signaling and involves the activation of protein tyrosine kinases, protein tyrosine phosphatases, and downstream effectors including phosphatidylinositol-3 (PI-3) kinase. Relatively little is
known of the role of lipid phosphatases in the control of ITAM signaling and inflammation. A heterologous COS7 cell system was used to examine the roles played by PI-3 kinase and the
dual-specificity phosphatase, phosphatase and tensin homolog deleted on
chromosome 10 (PTEN), in the signal transduction pathway leading to
Fc receptor IIA-mediated phagocytosis and the activation of Rac.
The expression of wildtype PTEN completely abrogated the phagocytosis
of immunoglobulin-G-sensitized sheep red blood cells, as
compared with the catalytically inactive mutant of PTEN, which had no
effect. This is the first direct evidence that PTEN, an inositol 3'
phosphatase, regulates Fc receptor-mediated phagocytosis, an
ITAM-based signaling event. The data suggest that PTEN exerts control
over phagocytosis potentially by controlling the downstream
conversion of guanosine diphosphate-Rac to guanosine triphosphate-Rac
following ITAM stimulation.
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