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Activation of p38 MAPK is required for ligand‐induced Class A scavenger receptor expression
Author(s) -
Kavanagh Lindsay Erin,
Nikolic Dejan,
Post Steven
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.a113-b
Subject(s) - scavenger receptor , kinase , microbiology and biotechnology , mapk/erk pathway , p38 mitogen activated protein kinases , signal transduction , internalization , chemistry , protein kinase a , mitogen activated protein kinase , receptor , extracellular , biology , biochemistry , lipoprotein , cholesterol
Class A Scavenger Receptors (SR‐A) mediate the internalization of a variety of polyanionic proteins (e.g., modified LDL, bacteria) and adhesion to modified extracellular matrix. Previous studies demonstrated that SR‐A expression and function are regulated by SR‐A ligands. In this study, we determined the importance of specific intracellular signaling pathways in ligand‐dependent regulation of SR‐A expression. For this, we incubated mouse peritoneal macrophages (MPM) with the SR‐A specific ligand AcLDL in the presence or absence of specific signaling pathway inhibitors. Activation of specific signaling proteins and changes in SR‐A protein were assessed by western blotting cell lysates with antibodies to SR‐A or the activated‐state of specific signaling proteins. We found that incubating MPM with acetylated‐LDL (AcLDL), but not native LDL, for 24 hrs dose‐dependently increased SR‐A expression. Incubation of MPM with AcLDL was associated with a rapid activation of the mitogen activated protein kinases (MAPK) extracellular signal‐regulated kinase (ERK1/2), cJun N‐terminal kinase (JNK), and p38 kinase. To determine the importance of MAPK activation in ligand‐dependent regulation of SR‐A expression, MPM were treated with specific inhibitors of ERK1/2, JNK, and p38 prior to incubating with AcLDL. Ligand‐induced SR‐A expression was not affected by either ERK1/2 or JNK inhibitors but was abolished by pretreating cells with the p38 kinase inhibitor. Overall, these results indicate that ligand binding to SR‐A activates multiple intracellular signaling pathways. However, ligand‐induced SR‐A expression specifically requires activation of p38 MAPK. ( Supported by grants from the NIH and AHA )