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Blood, 1 May 2002, Vol. 99, No. 9, pp. 3188-3196
HEMATOPOIESIS
Role of protein kinase C in the phosphorylation of CD33
(Siglec-3) and its effect on lectin activity
Kay Grobe and
Leland D. Powell
From the Departments of Medicine and Cellular and
Molecular Medicine, Glycobiology Research and Training Center,
University of California San Diego, La Jolla (K.G. and L.D.P.); and the
Department of Medicine, UCLA-Olive View Medical Center, Sylmar, CA
(L.D.P.).
CD33 (Siglec-3) is a marker of myeloid progenitor cells, mature
myeloid cells, and most myeloid leukemias. Although its biologic role
remains unknown, it has been demonstrated to function as a sialic
acid-specific lectin and a cell adhesion molecule. Many of the Siglecs
(including CD33) have been reported to be tyrosine phosphorylated in
the cytosolic tails under specific stimulation conditions. Here we
report that CD33 is also a serine/threonine phosphoprotein, containing
at least 2 sites of serine phosphorylation in its cytoplasmic domain,
catalyzed by protein kinase C (PKC). Phosphorylation could be augmented
by exposure to the protein kinase-activating cytokines interleukin 3, erythropoietin, or granulocyte-macrophage colony-stimulating factor, in
a cytokine-dependent cell line, TF-1. The CD33 cytoplasmic tail was
phosphorylated by PKC in vitro, in a Ca++/lipid-dependent
manner. CHOK1 cells stably expressing CD33 with cytoplasmic tails of
various length also showed phorbol myristate acetate
(PMA)-dependent phosphorylation of CD33. Inhibition of CD33
phosphorylation with pharmacologic agents resulted in an increase of
sialic acid-dependent rosette formation. Furthermore, the occupancy of
the lectin site affected its basal level of phosphorylation. Rosette
formation by COS cells expressing a form of CD33 lacking its
cytoplasmic domain was not affected by these same agents. These data
indicate that CD33 is a phosphoprotein, that its phosphorylation may be
controlled by PKC downstream of cytokine stimulation, and that its
phosphorylation is cross-regulated with its lectin activity. Notably,
although this is the first example of serine/threonine phosphorylation
in the subfamily of CD33-like Siglecs, some of the other members also
have putative target sites in their cytoplasmic tails.
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