The N-terminal region of ABC50 interacts with eukaryotic initiation factor eIF2 and is a target for regulatory phosphorylation by CK2

TY - JOUR

T1 - The N-terminal region of ABC50 interacts with eukaryotic initiation factor eIF2 and is a target for regulatory phosphorylation by CK2

AU - Paytubi, Sonia

AU - Morrice, Nicholas A.

AU - Boudeau, Jerome

AU - Proud, Christopher G.

PY - 2008

Y1 - 2008

N2 - ABC50 is an ABC (ATP-binding cassette) protein which, unlike most ABC proteins, lacks membrane-spanning domains. ABC50 interacts with eIF2 (eukaryotic initiation factor 2), a protein that plays a key role in translation initiation and in its control, and in regulation of ribosomes. Here, we establish that the interaction of ABC50 with eIF2 involves features in the N-terminal domain of ABC50, the region of ABC50 that differs most markedly from other ABC proteins. This region also shows no apparent similarity to the eIF2-binding domains of other partners of eIF2. In contrast, the N-terminus of ABC50 cannot bind to ribosomes by itself, but it can in conjunction with one of the nucleotide-binding domains. We demonstrate that ABC50 is a phosphoprotein and is phosphorylated at two sites by CK2. These sites, Ser-109 and Ser-140, lie in the N-terminal part of ABC50 but are not required for the binding of ABC50 to eIF2. Expression of a mutant of ABC50 in which both sites are mutated to alanine markedly decreased the association of eIF2 with 80S ribosomal and polysomal fractions.

AB - ABC50 is an ABC (ATP-binding cassette) protein which, unlike most ABC proteins, lacks membrane-spanning domains. ABC50 interacts with eIF2 (eukaryotic initiation factor 2), a protein that plays a key role in translation initiation and in its control, and in regulation of ribosomes. Here, we establish that the interaction of ABC50 with eIF2 involves features in the N-terminal domain of ABC50, the region of ABC50 that differs most markedly from other ABC proteins. This region also shows no apparent similarity to the eIF2-binding domains of other partners of eIF2. In contrast, the N-terminus of ABC50 cannot bind to ribosomes by itself, but it can in conjunction with one of the nucleotide-binding domains. We demonstrate that ABC50 is a phosphoprotein and is phosphorylated at two sites by CK2. These sites, Ser-109 and Ser-140, lie in the N-terminal part of ABC50 but are not required for the binding of ABC50 to eIF2. Expression of a mutant of ABC50 in which both sites are mutated to alanine markedly decreased the association of eIF2 with 80S ribosomal and polysomal fractions.

KW - ATP-Binding Cassette Transporters

KW - Alanine

KW - Binding Sites

KW - Casein Kinase II

KW - Cell Line

KW - Escherichia coli

KW - Eukaryotic Initiation Factor-2

KW - Humans

KW - Phosphoamino Acids

KW - Phosphorylation

KW - Plasmids

KW - Protein Binding

KW - Protein Biosynthesis

KW - Protein Structure, Tertiary

KW - Serine

U2 - 10.1042/BJ20070811

DO - 10.1042/BJ20070811

M3 - Article

C2 - 17894550

SN - 0264-6021

VL - 409

SP - 223

EP - 231

JO - Biochemical Journal

JF - Biochemical Journal

IS - 1

ER -