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An isoform‐specific PDZ‐binding motif targets type I PIP5 kinase beta to the uropod and controls polarization of neutrophil‐like HL60 cells
Author(s) -
Mañes Santos,
Fuentes Gloria,
Peregil Rosa M.,
Rojas Ana M.,
Lacalle Rosa Ana
Publication year - 2010
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/fj.09-153106
Subject(s) - pdz domain , microbiology and biotechnology , ezrin , chemotaxis , scaffold protein , biology , signal transduction , biochemistry , cytoskeleton , receptor , cell
Type I phosphatidylinositol 4‐phosphate 5‐kinase (PIP5KI)‐β participates in establishing polarity during leukocyte chemotaxis. Its final 83 amino acids localize PIP5KIβ to the uropod of chemotaxing neutrophils and T cells, and interact with ezrin‐radixinmoesin (ERM) proteins and EBP50 (4.1‐ERM‐binding phosphoprotein 50), a scaffold protein with 2 PDZ (PSD‐95, disc large, ZO‐1) domains. The structural motifs at the PIP5KIβ C terminus that confer signaling specificity are, nonetheless, unknown. We show that the last 4 residues of PIP5KIβ constitute an atypical PDZ‐binding motif, which steers PIP5KIβ to the uropod by binding to both EBP50 PDZ domains. Molecular modeling and mutagenesis indicated that PDZ‐binding motif is necessary for PIP5KIβ localization and for chemoattractant‐induced neutrophil polarization. Polarity in cells that express PIP5KIβ mutants lacking the PDZ‐binding motif was restored by overexpression of PIP5KIβ, but not of PIP5KIγ_i2, another isoform that localizes to the neutrophil uropod. Our results identify an isoform‐specific PDZ‐binding motif in PIP5KIβ, which confers specificity for PIP5KIβ signaling at the uropod during leukocyte chemotaxis.—Mañes, S., Fuentes, G., Peregil, R. M., Rojas, A. M., Lacalle, R. A. An isoform‐specific PDZ‐binding motif targets type I PIP5 kinase beta to the uropod and controls polarization of neutrophil‐like HL60 cells. FASEB J . 24, 3381–3392 (2010). www.fasebj.org