Details

Autor(en) / Beteiligte

• See, Raymond H
• Caday-Malcolm, Rosalinda A
• Singaraja, Roshni R
• Zhou, Steven
• Silverston, Anthony
• Huber, Mary T
• Moran, Josh
• James, Erick R
• Janoo, Rozmin
• Savill, Jane M
• Rigot, Veronique
• Zhang, Lin-Hua
• Wang, Minghan
• Chimini, Giovanna
• Wellington, Cheryl L
• Tafuri, Sherrie R
• Hayden, Michael R

Titel

Protein Kinase A Site-specific Phosphorylation Regulates ATP-binding Cassette A1 (ABCA1)-mediated Phospholipid Efflux

Ist Teil von

• The Journal of biological chemistry, 2002-11, Vol.277 (44), p.41835-41842

Ort / Verlag

United States: American Society for Biochemistry and Molecular Biology

Erscheinungsjahr

2002

Quelle

MEDLINE

Beschreibungen/Notizen

• ATP-binding cassette A1 (ABCA1) is a key mediator of cholesterol and phospholipid efflux to apolipoprotein particles. We show that ABCA1 is a constitutively phosphorylated protein in both RAW macrophages and in a human embryonic kidney cell line expressing ABCA1. Furthermore, we demonstrate that phosphorylation of ABCA1 is mediated by protein kinase A (PKA) or a PKA-like kinase in vivo . Through site-directed mutagenesis studies of consensus PKA phosphorylation sites and in vitro PKA kinase assays, we show that Ser-1042 and Ser-2054, located in the nucleotide binding domains of ABCA1, are major phosphorylation sites for PKA. ApoA-I-dependent phospholipid efflux was decreased significantly by mutation of Ser-2054 alone and Ser-1042/Ser-2054 but was not significantly impaired with Ser-1042 alone. The mechanism by which ABCA1 phosphorylation affected ApoA-I-dependent phospholipid efflux did not involve either alterations in ApoA-I binding or changes in ABCA1 protein stability. These studies demonstrate a novel serine (Ser-2054) on the ABCA1 protein crucial for PKA phosphorylation and for regulation of ABCA1 transporter activity.