Rab24 is an atypical member of the Rab GTPase family. Deficient GTPase activity, GDP dissociation inhibitor interaction, and prenylation of Rab24 expressed in cultured cells.
The function of Rab24 is currently unknown, but other members of the Rab GTPase family are known to participate in various protein trafficking pathways. Rab proteins are thought to cycle on and off vesicle membranes in conjunction with changes in their guanine nucleotide state. The present studies indicate that Rab24 possesses several unusual characteristics that distinguish it from other Rab proteins. 1) Based on [(32)P]orthophosphate labeling of protein-bound nucleotide, Rab24 exists predominantly in the GTP state when expressed in cultured cells. The low GTPase activity is related to the presence of serine instead of glutamine at the position cognate to Ras Gln-61. 2) Posttranslational geranylgeranylation of Rab24, determined by metabolic labeling or detergent partitioning assays, is inefficient when compared with other Rabs ending with the common CXC and CC carboxyl-terminal motifs. This is partly due to the presence of two histidines distal to the target cysteines, but also involves other unidentified features. 3) Most of the Rab24 in the cytoplasmic compartment of cultured cells is not associated with Rab GDP dissociation inhibitors. These findings indicate that, if Rab24 functions in vesicular transport processes, it may operate through a novel mechanism that does not depend on GTP hydrolysis or GDP dissociation inhibitor-mediated recycling.
Erdman
R A
RA
Weis Center for Research, Penn State College of Medicine, Danville, Pennsylvania 17822, USA.
Shellenberger
K E
KE
Overmeyer
J H
JH
Maltese
W A
WA
D000595:Amino Acid Sequence; D002460:Cell Line; D005455:Fluorescent Antibody Technique; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D017368:Protein Prenylation; D011499:Protein Processing, Post-Translational; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D016415:Sequence Alignment; D020691:rab GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*
D020730:Guanine Nucleotide Dissociation Inhibitors; D016271:Proto-Oncogene Proteins c-myc; D011994:Recombinant Proteins; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; C086224:Rab24 protein, mouse; D020691:rab GTP-Binding Proteins