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Engagement of P‐selectin Glycoprotein Ligand‐1 (PSGL‐1) induces interactions with the actin cytoskeleton
Author(s) -
Milenkovic Marija,
Snapp Karen R.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a649
Subject(s) - cytoskeleton , glycoprotein , actin , actin cytoskeleton , microbiology and biotechnology , chemistry , ligand (biochemistry) , receptor , biology , biochemistry , cell
P‐selectin glycoprotein ligand‐1 (PSGL‐1) is a well‐studied P‐selectin counter receptor. Its role as a rolling receptor has been well established, and interactions between PSGL‐1 and P‐selectin are known to be critical for a strong inflammatory response. Involvement of PSGL‐1 in signal transduction after P‐selectin engagement is not well known. The purpose of this study was to investigate potential downstream events following PSGL‐1 ligation by either a function blocking monoclonal antibody (KPL‐1) or P‐selectin. Crosslinking PSGL‐1 on HL60 cells with KPL‐1, which binds to the P‐selectin binding site on PSGL‐1, induces PSGL‐1 association with the actin cytoskeleton. Conversely, crosslinking of PSGL‐1 with KPL‐2, an antibody that recognizes a sequence on PSGL‐1 near the trans‐membrane domain, did not. We have shown that interactions between PSGL‐1 and the actin cytoskeleton are required for rolling on P‐selectin. To determine the potential pathway that induced associations with the actin cytoskeleton, cells were pre‐incubated with various pharmacological inhibitors prior to crosslinking. Reagents tested included inhibitors of tyrosine‐specific protein kinases (Genistein), p38 kinase (SB 203580), MAP kinase kinase (PD 98059), protein kinase C (Calphostin C), and Syk (Piceatannol). The results from this investigation will help us define the intracellular signaling pathway required for actin cytoskeletal rearrangement following PSGL‐1 ligation. [This work was supported by NIH R01 GM60563 and T32HL007829].