PMID- 10490598
OWN - NLM
STAT- MEDLINE
DCOM- 20000203
LR  - 20190508
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 19
IP  - 10
DP  - 1999 Oct
TI  - The Borgs, a new family of Cdc42 and TC10 GTPase-interacting proteins.
PG  - 6585-97
AB  - The Rho family of GTPases plays key roles in the regulation of cell motility and 
      morphogenesis. They also regulate protein kinase cascades, gene expression, and
      cell cycle progression. This multiplicity of roles requires that the Rho GTPases 
      interact with a wide variety of downstream effector proteins. An understanding of
      their functions at a molecular level therefore requires the identification of the
      entire set of such effectors. Towards this end, we performed a two-hybrid screen 
      using the TC10 GTPase as bait and identified a family of putative effector
      proteins related to MSE55, a murine stromal and epithelial cell protein of 55
      kDa. We have named this family the Borg (binder of Rho GTPases) proteins.
      Complete open reading frames have been obtained for Borg1 through Borg3. We
      renamed MSE55 as Borg5. Borg1, Borg2, Borg4, and Borg5 bind both TC10 and Cdc42
      in a GTP-dependent manner. Surprisingly, Borg3 bound only to Cdc42. An intact
      CRIB (Cdc42, Rac interactive binding) domain was required for binding. No
      interaction of the Borgs with Rac1 or RhoA was detectable. Three-hemagglutinin
      epitope (HA(3))-tagged Borg3 protein was mostly cytosolic when expressed
      ectopically in NIH 3T3 cells, with some accumulation in membrane ruffles. The
      phenotype induced by Borg3 was reminiscent of that caused by an inhibition of Rho
      function and was reversed by overexpression of Rho. Surprisingly, it was
      independent of the ability to bind Cdc42. Borg3 also inhibited Jun kinase
      activity by a mechanism that was independent of Cdc42 binding. HA(3)-Borg3
      expression caused substantial delays in the spreading of cells on fibronectin
      surfaces after replating, and the spread cells lacked stress fibers. We propose
      that the Borg proteins function as negative regulators of Rho GTPase signaling.
FAU - Joberty, G
AU  - Joberty G
AD  - Markey Center for Cell Signaling and Department of Pharmacology, University of
      Virginia, Charlottesville, Virginia 22908, USA. gmj4h@virginia.edu
FAU - Perlungher, R R
AU  - Perlungher RR
FAU - Macara, I G
AU  - Macara IG
LA  - eng
SI  - GENBANK/AF163840
SI  - GENBANK/AF164118
SI  - GENBANK/AF164119
SI  - GENBANK/AF165114
GR  - CA 56300/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Blood Proteins)
RN  - 0 (CDC42EP2 protein, human)
RN  - 0 (CDC42EP4 protein, human)
RN  - 0 (Cdc42ep5 protein, mouse)
RN  - 0 (GTP Phosphohydrolase Activators)
RN  - 0 (GTP-Binding Protein Regulators)
RN  - 0 (Recombinant Proteins)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.6.1.- (GTP Phosphohydrolases)
RN  - EC 3.6.1.- (RHOQ protein, human)
RN  - EC 3.6.1.- (Rhoq protein, mouse)
RN  - EC 3.6.5.2 (cdc42 GTP-Binding Protein)
RN  - EC 3.6.5.2 (rho GTP-Binding Proteins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Binding Sites
MH  - Blood Proteins
MH  - Cell Size
MH  - *GTP Phosphohydrolase Activators
MH  - GTP Phosphohydrolases
MH  - *GTP-Binding Protein Regulators
MH  - Gene Expression
MH  - Gene Library
MH  - JNK Mitogen-Activated Protein Kinases
MH  - Mice
MH  - Mitogen-Activated Protein Kinases/antagonists & inhibitors
MH  - Molecular Sequence Data
MH  - Protein Binding
MH  - Protein Structure, Tertiary
MH  - Recombinant Proteins/metabolism
MH  - Sequence Homology, Amino Acid
MH  - Signal Transduction
MH  - Tissue Distribution
MH  - Two-Hybrid System Techniques
MH  - cdc42 GTP-Binding Protein/metabolism
MH  - rho GTP-Binding Proteins/*metabolism
PMC - PMC84628
EDAT- 1999/09/22 00:00
MHDA- 1999/09/22 00:01
CRDT- 1999/09/22 00:00
PHST- 1999/09/22 00:00 [pubmed]
PHST- 1999/09/22 00:01 [medline]
PHST- 1999/09/22 00:00 [entrez]
AID - 10.1128/mcb.19.10.6585 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1999 Oct;19(10):6585-97. doi: 10.1128/mcb.19.10.6585.