Science, Vol 262, Issue 5138, 1436-1440
Copyright © 1993 by American Association for the Advancement of Science
Analysis of CD36 binding domains: ligand specificity controlled by dephosphorylation of an ectodomain
AS Asch,
I Liu,
FM Briccetti,
JW Barnwell,
F Kwakye-Berko,
A Dokun,
J Goldberger,
and
M Pernambuco
Division of Hematology-Oncology, Cornell University Medical College, New York, NY 10021.
The protein CD36 is a membrane receptor for thrombospondin (TSP), malaria-infected erythrocytes, and collagen. Three functional sequences were identified within a single disulfide loop of CD36: one that mediates TSP binding (amino acids 87 to 99) and two that support malarial cytoadhesion (amino acids 8 to 21 and 97 to 110). One of these peptides (p87-99) is a consensus protein kinase C (PKC) phosphorylation site. Dephosphorylation of constitutively phosphorylated CD36 in resting platelets and a megakaryocytic cell line led to the loss of collagen adhesion and platelet reactivity to collagen, with a reciprocal increase in TSP binding. PKC-mediated phosphorylation of this ectodomain resulted in a loss of TSP binding and the reciprocal acquisition of collagen binding. In site-directed mutagenesis studies, when the threonine phosphorylation site was changed to alanine, CD36 was expressed in a dephosphorylated state and bound to TSP constitutively.
