Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Interaction of the Ras-related protein associated with diabetes rad and the putative tumor metastasis suppressor NM23 provides a novel mechanism of GTPase regulation.

Rad is the prototypic member of a new class of Ras-related GTPases. Purification of the GTPase-activating protein (GAP) for Rad revealed nm23, a putative tumor metastasis suppressor and a development gene in Drosophila. Antibodies against nm23 depleted Rad-GAP activity from human skeletal muscle cytosol, and bacterially expressed nm23 reconstituted the activity. The GAP activity of nm23 was specific for Rad, was absent with the S105N putative dominant negative mutant of Rad, and was reduced with mutations of nm23. In the presence of ATP, GDP.Rad was also reconverted to GTP.Rad by the nucleoside diphosphate (NDP) kinase activity of nm23. Simultaneously, Rad regulated nm23 by enhancing its NDP kinase activity and decreasing its autophosphorylation. Melanoma cells transfected with wild-type Rad, but not the S105N-Rad, showed enhanced DNA synthesis in response to serum; this effect was lost with coexpression of nm23. Thus, the interaction of nm23 and Rad provides a potential novel mechanism for bidirectional, bimolecular regulation in which nm23 stimulates both GTP hydrolysis and GTP loading of Rad whereas Rad regulates activity of nm23. This interaction may play important roles in the effects of Rad on glucose metabolism and the effects of nm23 on tumor metastasis and developmental regulation.

Pubmed ID: 10611312 RIS Download

Mesh terms: Animals | DNA | Diabetes Mellitus | Enzyme Activation | GTP Phosphohydrolases | Genes, Tumor Suppressor | Glucose | Guanosine Triphosphate | Humans | Immediate-Early Proteins | Models, Biological | Monomeric GTP-Binding Proteins | NM23 Nucleoside Diphosphate Kinases | Neoplasm Metastasis | Nucleoside-Diphosphate Kinase | Protein Binding | Rats | Rats, Sprague-Dawley | Transcription Factors | ras Proteins

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NIDDK NIH HHS, Id: T32 DK007260
  • Agency: NIDDK NIH HHS, Id: P30 DK036836
  • Agency: NIDDK NIH HHS, Id: F32 DK009193
  • Agency: NIDDK NIH HHS, Id: DK 45935
  • Agency: NCI NIH HHS, Id: R01 CA037393
  • Agency: NIDDK NIH HHS, Id: R01 DK047919
  • Agency: NIDDK NIH HHS, Id: R01 DK045935
  • Agency: NIDDK NIH HHS, Id: R01 DK 47919
  • Agency: NCI NIH HHS, Id: R01 CA 37393

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

We have not found any resources mentioned in this publication.