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A Cytoplasmic Acidic Amino Acid Motif Mediates PI3‐Kinase‐Sensitive Cell Adhesion and Surface Localization of Class A Scavenger Receptors
Author(s) -
Post Steven,
Cholewa Jill M.,
Nikolic Dejan M.
Publication year - 2009
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.23.1_supplement.945.2
Subject(s) - internalization , cytoplasm , scavenger receptor , cell adhesion , microbiology and biotechnology , receptor , amino acid , ligand (biochemistry) , biochemistry , chemistry , biology , cell , lipoprotein , cholesterol
Class A scavenger receptors (SR‐A) bind a diverse array of ligands and mediate ligand internalization or cell adhesion. The role of specific cytoplasmic domains in coupling SR‐A to ligand internalization or cell adhesion is not clear. The importance of the cytoplasmic tail in regulating SR‐A function was shown by deleting all but six cytoplasmic amino acids (SR‐AΔ 1‐49 ). Although SR‐AΔ 1‐49 displayed increased surface localization and mediated cell adhesion, it did not internalize ligand. Moreover, in contrast to the full‐length receptor, cell surface expression and cell adhesion mediated by SR‐AΔ 1‐49 was independent of PI3‐kinase (PI3K) activation. To examine the importance of specific amino acids in the cytoplasmic tail of SR‐A, potential regulatory sites were mutated and mutant receptors expressed in HEK cells. Changing the acidic amino acids within a conserved ‐EDAD‐ domain to their amide derivatives (SR‐A QNAN ) selectively altered SR‐A localization and regulation. Similar to SR‐AΔ 1‐49 , cell surface localization and cell adhesion mediated by SR‐A QNAN was independent of PI3K activation. However, ligand internalization mediated by SR‐A QNAN was similar to that of the full‐length receptor. Our results show that acidic amino acids in a cytoplasmic ‐EDAD‐ domain are required for PI3K‐dependent regulation of SR‐A surface localization and are differentially involved in regulating SR‐A function.