Activation-dependent changes in human platelet PECAM-1: phosphorylation, cytoskeletal association, and surface membrane redistribution.
PECAM-1 is a recently described member of the immunoglobulin gene (Ig) superfamily that is expressed on the surface on platelets, several leukocyte subsets, and at the endothelial cell intracellular junction. Recent studies have shown that the extracellular domain of PECAM-1, which is comprised of 6 Ig-like homology units, participates in mediating cell-cell adhesion, plays a role in initiating endothelial cell contact, and may later serve to stabilize the endothelial cell monolayer. PECAM-1 also has a relatively large 108 amino acid cytoplasmic domain, with potential sites for phosphorylation, lipid modification, and other posttranslational events that could potentially modulate its adhesive function or regulate its subcellular distribution. Virtually nothing is known about the contribution of the intracellular region of the PECAM-1 molecule to either of these cellular processes. Using human platelets as a model, we now demonstrate that PECAM-1 becomes highly phosphorylated in response to cellular activation, and coincident with phosphorylation associates with the cytoskeleton of activated, but not resting, platelets. The engagement of PECAM-1 with the platelet cytoskeleton enables it to move large distances within the plane of the membrane of fully-spread, adherent platelets. This redistribution may similarly account for the ability of PECAM-1 to localize to the intracellular borders of endothelial cells once cell-cell contact has been achieved.
Newman
P J
PJ
Blood Research Institute, Blood Center of Southeastern Wisconsin, Milwaukee.
Hillery
C A
CA
Albrecht
R
R
Parise
L V
LV
Berndt
M C
MC
Mazurov
A V
AV
Dunlop
L C
LC
Zhang
J
J
Rittenhouse
S E
SE
D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism / Q000648:ultrastructure; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism*; D006801:Humans; D016253:Microscopy, Immunoelectron; D010766:Phosphorylation; D015539:Platelet Activation / Q000502:physiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1
D015214:Antigens, Differentiation, Myelomonocytic; D015815:Cell Adhesion Molecules; D019408:Platelet Endothelial Cell Adhesion Molecule-1