PMID- 3355599
OWN - NLM
STAT- MEDLINE
DCOM- 19880510
LR  - 20190623
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 37
IP  - 7
DP  - 1988 Apr 1
TI  - Formation and stability of vincristine-tubulin complex in kidney cytosols. Role 
      of GTP and GTP hydrolysis.
PG  - 1251-7
AB  - Vincristine-tubulin complex formed in the 100,000 g fraction of mouse kidney 
      dissociated rapidly at 37 degrees in the absence of guanosine-5'-triphosphate 
      (GTP). In the presence of 2 mM GTP, there was a substantial (2.8-fold) increase 
      in complex stability; NaF (100 mM) but not beta-glycerophosphate (1 mM) also 
      reduced the rate of dissociation. Further, complex was stabilized by other 
      ribonucleoside-5'-triphosphates (but not their respective 5'-monophosphates), and 
      a nonhydrolyzable analogue of GTP. Stability of the VCR-tubulin complex formed in 
      cytosol from kidney and separated from unbound VCR and GTP by gel filtration was 
      influenced by the concentration of GTP. These results appear not to be a 
      consequence of denaturation of tubulin during incubation, as VCR binding activity 
      remained constant under experimental conditions both in the presence and after 
      the removal of GTP. Further, the rate of formation of the VCR-tubulin complex in 
      kidney was also influenced by the concentration of GTP and was increased by the 
      addition of NaF. In the absence of added GTP, virtually no complex was isolated. 
      ATP, CTP, or ITP has little effect on complex formation, suggesting that the 
      effect may be GTP specific. These data suggest that the destabilizing activity in 
      cytosols prepared from mouse kidney, and the failure to form a stable VCR-tubulin 
      complex in kidney, are in part the consequence of rapid hydrolysis of GTP by a 
      pyrophosphohydrolase. Direct measurement of the hydrolysis of GTP showed that the 
      activity in kidney (9.26 nmol/min/mg protein) was 9.3-fold greater than in tumor 
      extracts.
FAU - Bowman, L C
AU  - Bowman LC
AD  - Division of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, 
      TN 38101.
FAU - Houghton, J A
AU  - Houghton JA
FAU - Houghton, P J
AU  - Houghton PJ
LA  - eng
GR  - CA 23099/CA/NCI NIH HHS/United States
GR  - CA 23944/CA/NCI NIH HHS/United States
GR  - CA 38933/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Tubulin)
RN  - 5J49Q6B70F (Vincristine)
RN  - 86-01-1 (Guanosine Triphosphate)
SB  - IM
MH  - Animals
MH  - Binding Sites
MH  - Cytosol/*metabolism
MH  - Female
MH  - Guanosine Triphosphate/metabolism/*pharmacology
MH  - Hydrolysis
MH  - In Vitro Techniques
MH  - Kidney/*metabolism
MH  - Mice
MH  - Mice, Inbred CBA
MH  - Tubulin/*metabolism
MH  - Vincristine/*metabolism
EDAT- 1988/04/01 00:00
MHDA- 1988/04/01 00:01
CRDT- 1988/04/01 00:00
PHST- 1988/04/01 00:00 [pubmed]
PHST- 1988/04/01 00:01 [medline]
PHST- 1988/04/01 00:00 [entrez]
AID - 0006-2952(88)90778-2 [pii]
AID - 10.1016/0006-2952(88)90778-2 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 1988 Apr 1;37(7):1251-7. doi: 10.1016/0006-2952(88)90778-2.