Different domains of mammalian ADP-ribosylation factor 1 mediate interaction with selected target proteins.
Mammalian ADP-ribosylation factor 1 (mARF1) is a small GTP-binding protein that is activated by a Golgi guanine nucleotide exchange factor. Once bound to the Golgi membranes in the GTP form, mARF1 initiates the recruitment of the adaptor protein 1 (AP-1) complex and coatomer (COPI) onto these membranes and activates phospholipase D1 (PLD1). To map the domains of mARF1 that are important for these activities, we constructed chimeras between mARF1 and Saccharomyces cerevisiae ARF2, which functions poorly in all of these processes except COPI recruitment. The carboxyl half of mARF1 (amino acids 95-181) was essential for activation by the Golgi guanine nucleotide exchange factor, whereas a separate domain (residues 35-94) was required to effectively activate PLD1 and to promote efficient AP-1 recruitment. Since residues 35-94 of mARF1 are critical for optimal activity in both PLD1 activation and AP-1 recruitment, we hypothesize that this region of ARF contains residues that interact with effector molecules.
Liang
J O
JO
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Sung
T C
TC
Morris
A J
AJ
Frohman
M A
MA
Kornfeld
S
S
D020727:ADP-Ribosylation Factors; D000262:Adenylyl Cyclases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors; D006801:Humans; D008099:Liver / Q000166:cytology; D008969:Molecular Sequence Data; D010739:Phospholipase D / Q000378:metabolism; D017354:Point Mutation; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism
D002352:Carrier Proteins; D020662:Guanine Nucleotide Exchange Factors; D011506:Proteins; D011993:Recombinant Fusion Proteins; D018808:Transcription Factor AP-1; D010739:Phospholipase D; D019204:GTP-Binding Proteins; C486434:Arf2 protein, rat; D020727:ADP-Ribosylation Factors; C116688:ARF4 protein, human; D000262:Adenylyl Cyclases