PMID- 10445846
OWN - NLM
STAT- MEDLINE
DCOM- 19990907
LR  - 20191210
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 26
DP  - 1999 Jul 1
TI  - Cellular functions of TC10, a Rho family GTPase: regulation of morphology, signal
      transduction and cell growth.
PG  - 3831-45
AB  - The small Ras-related GTPase, TC10, has been classified on the basis of sequence 
      homology to be a member of the Rho family. This family, which includes the Rho,
      Rac and CDC42 subfamilies, has been shown to regulate a variety of apparently
      diverse cellular processes such as actin cytoskeletal organization,
      mitogen-activated protein kinase (MAPK) cascades, cell cycle progression and
      transformation. In order to begin a study of TC10 biological function, we
      expressed wild type and various mutant forms of this protein in mammalian cells
      and investigated both the intracellular localization of the expressed proteins
      and their abilities to stimulate known Rho family-associated processes. Wild type
      TC10 was located predominantly in the cell membrane (apparently in the same
      regions as actin filaments), GTPase defective (75L) and GTP-binding defective
      (31N) mutants were located predominantly in cytoplasmic perinuclear regions, and 
      a deletion mutant lacking the carboxyl terminal residues required for
      post-translational prenylation was located predominantly in the nucleus. The
      GTPase defective (constitutively active) TC10 mutant: (1) stimulated the
      formation of long filopodia; (2) activated c-Jun amino terminal kinase (JNK); (3)
      activated serum response factor (SRF)-dependent transcription; (4) activated
      NF-kappaB-dependent transcription; and (5) synergized with an activated
      Raf-kinase (Raf-CAAX) to transform NIH3T3 cells. In addition, wild type TC10
      function is required for full H-Ras transforming potential. We demonstrate that
      an intact effector domain and carboxyl terminal prenylation signal are required
      for proper TC10 function and that TC10 signals to at least two separable
      downstream target pathways. In addition, TC10 interacted with the actin-binding
      and filament-forming protein, profilin, in both a two-hybrid cDNA library screen,
      and an in vitro binding assay. Taken together, these data support a
      classification of TC10 as a member of the Rho family, and in particular, suggest 
      that TC10 functions to regulate cellular signaling to the actin cytoskeleton and 
      processes associated with cell growth.
FAU - Murphy, G A
AU  - Murphy GA
AD  - Department of Biochemistry, New York University Medical Center, New York 10016,
      USA.
FAU - Solski, P A
AU  - Solski PA
FAU - Jillian, S A
AU  - Jillian SA
FAU - Perez de la Ossa, P
AU  - Perez de la Ossa P
FAU - D'Eustachio, P
AU  - D'Eustachio P
FAU - Der, C J
AU  - Der CJ
FAU - Rush, M G
AU  - Rush MG
LA  - eng
GR  - CA42978/CA/NCI NIH HHS/United States
GR  - CA55008/CA/NCI NIH HHS/United States
GR  - CA63071/CA/NCI NIH HHS/United States
GR  - etc.
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Contractile Proteins)
RN  - 0 (DNA, Complementary)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Microfilament Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Pfn1 protein, mouse)
RN  - 0 (Profilins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Serum Response Factor)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
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.- (GTP-Binding Proteins)
RN  - EC 3.6.1.- (Rhoq protein, mouse)
RN  - EC 3.6.5.2 (cdc42 GTP-Binding Protein)
RN  - EC 3.6.5.2 (rac GTP-Binding Proteins)
RN  - EC 3.6.5.2 (rho GTP-Binding Proteins)
RN  - EC 3.6.5.2 (rhoA GTP-Binding Protein)
SB  - IM
MH  - 3T3 Cells
MH  - Amino Acid Sequence
MH  - Animals
MH  - COS Cells
MH  - Calcium-Calmodulin-Dependent Protein Kinases/metabolism
MH  - Cell Cycle Proteins/chemistry
MH  - Cell Division
MH  - Cell Size
MH  - Cell Transformation, Neoplastic
MH  - Chlorocebus aethiops
MH  - *Contractile Proteins
MH  - DNA, Complementary/genetics
MH  - DNA-Binding Proteins/metabolism
MH  - Enzyme Activation
MH  - GTP Phosphohydrolases/classification/deficiency/genetics/metabolism/*physiology
MH  - GTP-Binding Proteins/chemistry
MH  - JNK Mitogen-Activated Protein Kinases
MH  - Mice
MH  - Microfilament Proteins/metabolism
MH  - *Mitogen-Activated Protein Kinases
MH  - Molecular Sequence Data
MH  - Multigene Family
MH  - NF-kappa B/metabolism
MH  - Nuclear Proteins/metabolism
MH  - Profilins
MH  - Protein Binding
MH  - Recombinant Fusion Proteins/physiology
MH  - Sequence Alignment
MH  - Sequence Homology, Amino Acid
MH  - Serum Response Factor
MH  - Signal Transduction/*physiology
MH  - Transcription, Genetic
MH  - cdc42 GTP-Binding Protein
MH  - rac GTP-Binding Proteins
MH  - *rho GTP-Binding Proteins
MH  - rhoA GTP-Binding Protein
EDAT- 1999/08/13 00:00
MHDA- 1999/08/13 00:01
CRDT- 1999/08/13 00:00
PHST- 1999/08/13 00:00 [pubmed]
PHST- 1999/08/13 00:01 [medline]
PHST- 1999/08/13 00:00 [entrez]
AID - 10.1038/sj.onc.1202758 [doi]
PST - ppublish
SO  - Oncogene. 1999 Jul 1;18(26):3831-45. doi: 10.1038/sj.onc.1202758.