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Originally published In Press as doi:10.1074/jbc.M006537200 on November 30, 2000
J. Biol. Chem., Vol. 276, Issue 9, 6327-6336, March 2, 2001
Insufficient Phosphorylation Prevents Fc RIIB from Recruiting
the SH2 Domain-containing Protein-tyrosine Phosphatase SHP-1*
Renaud
Lesourne ,
Pierre
Bruhns,
Wolf H.
Fridman, and
Marc
Daëron§
From the Laboratoire d'Immunologie Cellulaire et Clinique, INSERM
U.255, Institut Curie, 75005 Paris, France
Fc RIIB are IgG receptors that inhibit
immunoreceptor tyrosine-based activation motif
(ITAM)-dependent cell activation. Inhibition depends on an
immunoreceptor tyrosine-based inhibition motif (ITIM) that is
phosphorylated upon Fc RIIB coaggregation with ITAM-bearing receptors
and recruits SH2 domain-containing phosphatases. Agarose bead-coated
phosphorylated ITIM peptides (pITIMs) bind in vitro the
single-SH2 inositol 5-phosphatases (SHIP1 and SHIP2) and the two-SH2
protein tyrosine phosphatases (SHP-1 and SHP-2). Phosphorylated Fc RIIB, however, recruit selectively SHIP1/2 in vivo. We
aimed here at explaining this discordance. We found that beads coated with low amounts of pITIM bound in vitro SHIP1, but not
SHP-1, i.e. behaved as phosphorylated Fc RIIB in
vivo. The reason is that SHP-1 requires its two SH2 domains to
bind on adjacent pITIMs. Consequently, the binding of SHP-1, but not of
SHIP1, increased with pITIM density on beads. When trying to increase
Fc RIIB phosphorylation in B cells and mast cells, we found that
concentrations of ligands optimal for Fc RIIB phosphorylation failed
to induce SHP-1 recruitment. SHP-1 was, however, recruited by Fc RIIB
when hyperphosphorylated following cell treatment with pervanadate. Our
data suggest that Fc RIIB phosphorylation may not be sufficient
in vivo to enable the recruitment of SHP-1 but that
(pathological?) conditions that would hyperphosphorylate Fc RIIB
might enable SHP-1 recruitment.
*
This work was supported in part by the Institut National de
la Santé et de la Recherche Médicale, the Institut Curie,
and the Association pour la Recherche sur le Cancer.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Recipient of a fellowship from the Ministère de
l'Enseignement Supérieur et de la Recherche.
§
To whom correspondence should be addressed: Laboratoire
d'Immunologie Cellulaire et Clinique, INSERM U. 255, Institut Curie, 26 rue d'Ulm, 75005 Paris, France. Tel.: 33-1-4432-4223; Fax: 33-1-4051-0420; E-mail: Marc.Daeron@curie.fr.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.
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