ELMOD2 is an Arl2 GTPase-activating protein that also acts on Arfs.
Regulatory GTPases in the Ras superfamily employ a cycle of alternating GTP binding and hydrolysis, controlled by guanine nucleotide exchange factors and GTPase-activating proteins (GAPs), as essential features of their actions in cells. Studies of these GAPs and guanine nucleotide exchange factors have provided important insights into our understanding of GTPase signaling and biology. Within the Ras superfamily, the Arf family is composed of 30 members in mammals, including 22 Arf-like (Arl) proteins. Much less is known about the mechanisms of cell regulation by Arls than by Arfs. We report the purification from bovine testis of an Arl2 GAP and its identity as ELMOD2, a protein with no previously described function. ELMOD2 is one of six human proteins that contain an ELMO domain, and a second member, ELMOD1, was also found to have Arl2 GAP activity. Surprisingly, ELMOD2 also exhibited GAP activity against Arf proteins even though it does not contain the canonical Arf GAP sequence signature. The broader specificity of ELMOD2, as well as the previously described role for ELMO1 and ELMO2 in linking Arf6 and Rac1 signaling, suggests that ELMO family members may play a more general role in integrating signaling pathways controlled by Arls and other GTPases.
Bowzard
J Bradford
JB
Department of Biochemistry, Center for Neurodegenerative Diseases, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Cheng
Dongmei
D
Peng
Junmin
J
Kahn
Richard A
RA
D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020690:GTPase-Activating Proteins; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D013737:Testis / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D020931:ran GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
D003598:Cytoskeletal Proteins; C522868:ELMOD1 protein, human; C512339:ELMOD2 protein, human; D020690:GTPase-Activating Proteins; D011994:Recombinant Proteins; C410130:ARL2 protein, human; D019204:GTP-Binding Proteins; D020727:ADP-Ribosylation Factors; D020830:rac1 GTP-Binding Protein; D020931:ran GTP-Binding Protein; D020742:rhoA GTP-Binding Protein