PMID- 10611312
OWN - NLM
STAT- MEDLINE
DCOM- 20000127
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 26
DP  - 1999 Dec 21
TI  - Interaction of the Ras-related protein associated with diabetes rad and the
      putative tumor metastasis suppressor NM23 provides a novel mechanism of GTPase
      regulation.
PG  - 14911-8
AB  - 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.
FAU - Zhu, J
AU  - Zhu J
AD  - Research Division, Joslin Diabetes Center, Department of Medicine, Harvard
      Medical School, One Joslin Place, Boston, MA 02215, USA.
FAU - Tseng, Y H
AU  - Tseng YH
FAU - Kantor, J D
AU  - Kantor JD
FAU - Rhodes, C J
AU  - Rhodes CJ
FAU - Zetter, B R
AU  - Zetter BR
FAU - Moyers, J S
AU  - Moyers JS
FAU - Kahn, C R
AU  - Kahn CR
LA  - eng
GR  - T32 DK007260/DK/NIDDK NIH HHS/United States
GR  - P30 DK036836/DK/NIDDK NIH HHS/United States
GR  - F32 DK009193/DK/NIDDK NIH HHS/United States
GR  - DK 45935/DK/NIDDK NIH HHS/United States
GR  - R01 CA037393/CA/NCI NIH HHS/United States
GR  - R01 DK047919/DK/NIDDK NIH HHS/United States
GR  - R01 DK045935/DK/NIDDK NIH HHS/United States
GR  - R01 DK 47919/DK/NIDDK NIH HHS/United States
GR  - R01 CA 37393/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (NM23 Nucleoside Diphosphate Kinases)
RN  - 0 (RRAD protein, human)
RN  - 0 (Rrad protein, mouse)
RN  - 0 (Rrad protein, rat)
RN  - 0 (Transcription Factors)
RN  - 86-01-1 (Guanosine Triphosphate)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.4.6 (NME1 protein, human)
RN  - EC 2.7.4.6 (Nme1 protein, mouse)
RN  - EC 2.7.4.6 (Nucleoside-Diphosphate Kinase)
RN  - EC 3.6.1.- (GTP Phosphohydrolases)
RN  - EC 3.6.5.2 (GEM protein, human)
RN  - EC 3.6.5.2 (Monomeric GTP-Binding Proteins)
RN  - EC 3.6.5.2 (ras Proteins)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - DNA/biosynthesis
MH  - Diabetes Mellitus/metabolism
MH  - Enzyme Activation
MH  - GTP Phosphohydrolases/*metabolism
MH  - Genes, Tumor Suppressor
MH  - Glucose/metabolism
MH  - Guanosine Triphosphate/*metabolism
MH  - Humans
MH  - Immediate-Early Proteins/metabolism
MH  - Models, Biological
MH  - Monomeric GTP-Binding Proteins/genetics/*metabolism
MH  - NM23 Nucleoside Diphosphate Kinases
MH  - Neoplasm Metastasis/genetics
MH  - Nucleoside-Diphosphate Kinase/genetics/*metabolism
MH  - Protein Binding
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Transcription Factors/genetics/*metabolism
MH  - ras Proteins/*metabolism
PMC - PMC24747
EDAT- 1999/12/28 00:00
MHDA- 1999/12/28 00:01
CRDT- 1999/12/28 00:00
PHST- 1999/12/28 00:00 [pubmed]
PHST- 1999/12/28 00:01 [medline]
PHST- 1999/12/28 00:00 [entrez]
AID - 10.1073/pnas.96.26.14911 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):14911-8. doi:
      10.1073/pnas.96.26.14911.