Publications [#64095] of Harold P. Erickson

Papers Published

1. Ushiyama, Shigeru and Laue, Thomas M. and Moore, Kevin L. and Erickson, Harold P. and McEver, Rodger P., Structural and functional characterization of monomeric soluble P-selectin and comparison with membrane P-selectin, Journal of Biological Chemistry, vol. 268 no. 20 (1993), pp. 15229 - 15237
   (last updated on 2007/04/15)

   Abstract:
   P-selectin is an adhesion receptor for leukocytes on thrombin-activated platelets and endothelial cells. It contains a NH₂-terminal carbohydrate-recognition domain, an epidermal growth factor motif, nine consensus repeats, a transmembrane domain, and a cytoplasmic tail. We expressed two soluble forms of P-selectin, one truncated after the ninth repeat (tPS) and the other lacking the transmembrane domain due to alternative RNA splicing (asPS). When visualized by electron microscopy, each was a monomeric rod-like structure with a globular domain at one end, whereas membrane P-selectin (mPS) from platelets formed rosettes with the globular domains facing outward. Sedimentation velocity and equilibrium studies confirmed that tPS and asPS were asymmetric monomers, whereas mPS was oligomeric. HL-60 cells adhered to immobilized tPS and asPS, although less efficiently than to mPS. ¹²⁵I-Labeled tPS and asPS bound to -25,000 sites/neutrophil and [similar to] 36,000 sites/HL-60 cell with an apparent Kd of 70 nM. Treatment of HL-60 cells with O-sialoglycoprotease eliminated the binding sites for asPS. We conclude that 1) P-selectin is a rigid, asymmetric protein; 2) monomeric soluble P-selectin binds to high affinity ligands with sialylated O-linked oligosaccharides on leukocytes; and 3) oligomerization of mPS enhances its avidity for leukocytes.