scholarly journals The carboxyl-terminal CXXX sequence of Gi alpha, but not Rab5 or Rab11, supports Ras processing and transforming activity

1993 ◽  
Vol 268 (16) ◽  
pp. 11548-11552
Author(s):  
A.D. Cox ◽  
S.M. Graham ◽  
P.A. Solski ◽  
J.E. Buss ◽  
C.J. Der
Keyword(s):  
Transforming Activity ◽  
Carboxyl Terminal

scholarly journals The transforming potential of the c-erbB-2 protein is regulated by its autophosphorylation at the carboxyl-terminal domain.

1991 ◽  
Vol 11 (2) ◽  
pp. 833-842 ◽  
Author(s):  
T Akiyama ◽  
S Matsuda ◽  
Y Namba ◽  
T Saito ◽  
K Toyoshima ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Kinase Activity ◽  
Cellular Transformation ◽  
Tyrosine Kinase Activity ◽  
Terminal Domain ◽  
Carboxyl Terminal Domain ◽  
Additional Mutation ◽  
Transforming Activity ◽  
Carboxyl Terminal ◽  
Autophosphorylation Site

The mutant c-erbB-2 protein with Glu instead of Val-659 exhibited transforming activity in NIH 3T3 cells. This protein showed enhanced tyrosine kinase activity in vitro and enhanced autophosphorylation at Tyr-1248 located proximal to the carboxyl terminus. Enhanced tyrosine phosphorylation of several cellular proteins was detected in cells expressing the Glu-659 c-erbB-2 protein. Introduction of an additional mutation at the ATP-binding site (Lys-753 to Met) of this protein resulted in abolition of its transforming ability. These data indicate that the transforming potential of c-erbB-2 is closely correlated with elevated tyrosine kinase activity of the gene product. To investigate the role of autophosphorylation in cell transformation, we introduced an additional mutation at the autophosphorylation site of the Glu-659 c-erbB-2 protein (Tyr-1248 to Phe). This mutant protein exhibited lower tyrosine kinase activity and lower transforming activity. On the other hand, when the carboxyl-terminal 230 amino acid residues were deleted from the c-erbB-2 protein, the tyrosine kinase activity and cell-transforming activity of the protein were enhanced. Thus, the carboxyl-terminal domain, which contains the major autophosphorylation site, Tyr-1248, may regulate cellular transformation negatively and autophosphorylation may eliminate this negative regulation.

44-amino-acid E5 transforming protein of bovine papillomavirus requires a hydrophobic core and specific carboxyl-terminal amino acids

1988 ◽  
Vol 8 (10) ◽  
pp. 4071-4078
Author(s):  
B H Horwitz ◽  
A L Burkhardt ◽  
R Schlegel ◽  
D DiMaio
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Saturation Mutagenesis ◽  
Amino Acid Substitutions ◽  
Bovine Papillomavirus ◽  
Missense Mutations ◽  
Focus Formation ◽  
E5 Protein ◽  
Transforming Activity ◽  
Carboxyl Terminal

The 44-amino-acid E5 protein of bovine papillomavirus type 1 is the shortest known protein with transforming activity. To identify the specific amino acids required for in vitro focus formation in mouse C127 cells, we used oligonucleotide-directed saturation mutagenesis to construct an extensive collection of mutants with missense mutations in the E5 gene. Characterization of mutants with amino acid substitutions in the hydrophobic middle third of the E5 protein indicated that efficient transformation requires a stretch of hydrophobic amino acids but not a specific amino acid sequence in this portion of the protein. Many amino acids in the carboxyl-terminal third of the protein can also undergo substitution without impairment of focus-forming activity, but the amino acids at seven positions, including two cysteine residues that mediate dimer formation, appear essential for efficient transforming activity. These essential amino acids are the most well conserved among related fibropapillomaviruses. The small size of the E5 protein, its lack of similarity to other transforming proteins, and its ability to tolerate many amino acid substitutions implies that it transforms cells via a novel mechanism.

The transforming potential of the c-erbB-2 protein is regulated by its autophosphorylation at the carboxyl-terminal domain

1991 ◽  
Vol 11 (2) ◽  
pp. 833-842
Author(s):  
T Akiyama ◽  
S Matsuda ◽  
Y Namba ◽  
T Saito ◽  
K Toyoshima ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Kinase Activity ◽  
Cellular Transformation ◽  
Tyrosine Kinase Activity ◽  
Terminal Domain ◽  
Carboxyl Terminal Domain ◽  
Additional Mutation ◽  
Transforming Activity ◽  
Carboxyl Terminal ◽  
Autophosphorylation Site

The mutant c-erbB-2 protein with Glu instead of Val-659 exhibited transforming activity in NIH 3T3 cells. This protein showed enhanced tyrosine kinase activity in vitro and enhanced autophosphorylation at Tyr-1248 located proximal to the carboxyl terminus. Enhanced tyrosine phosphorylation of several cellular proteins was detected in cells expressing the Glu-659 c-erbB-2 protein. Introduction of an additional mutation at the ATP-binding site (Lys-753 to Met) of this protein resulted in abolition of its transforming ability. These data indicate that the transforming potential of c-erbB-2 is closely correlated with elevated tyrosine kinase activity of the gene product. To investigate the role of autophosphorylation in cell transformation, we introduced an additional mutation at the autophosphorylation site of the Glu-659 c-erbB-2 protein (Tyr-1248 to Phe). This mutant protein exhibited lower tyrosine kinase activity and lower transforming activity. On the other hand, when the carboxyl-terminal 230 amino acid residues were deleted from the c-erbB-2 protein, the tyrosine kinase activity and cell-transforming activity of the protein were enhanced. Thus, the carboxyl-terminal domain, which contains the major autophosphorylation site, Tyr-1248, may regulate cellular transformation negatively and autophosphorylation may eliminate this negative regulation.

scholarly journals Transforming Activity of the Rho Family GTPase, Wrch-1, a Wnt-regulated Cdc42 Homolog, Is Dependent on a Novel Carboxyl-terminal Palmitoylation Motif

2005 ◽  
Vol 280 (38) ◽  
pp. 33055-33065 ◽  
Author(s):  
Anastacia C. Berzat ◽  
Janice E. Buss ◽  
Emily J. Chenette ◽  
Carolyn A. Weinbaum ◽  
Adam Shutes ◽  
...  
Keyword(s):  
Transforming Activity ◽  
Rho Family ◽  
Carboxyl Terminal

scholarly journals 44-amino-acid E5 transforming protein of bovine papillomavirus requires a hydrophobic core and specific carboxyl-terminal amino acids.

1988 ◽  
Vol 8 (10) ◽  
pp. 4071-4078 ◽  
Author(s):  
B H Horwitz ◽  
A L Burkhardt ◽  
R Schlegel ◽  
D DiMaio
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Saturation Mutagenesis ◽  
Amino Acid Substitutions ◽  
Bovine Papillomavirus ◽  
Missense Mutations ◽  
Focus Formation ◽  
E5 Protein ◽  
Transforming Activity ◽  
Carboxyl Terminal

The 44-amino-acid E5 protein of bovine papillomavirus type 1 is the shortest known protein with transforming activity. To identify the specific amino acids required for in vitro focus formation in mouse C127 cells, we used oligonucleotide-directed saturation mutagenesis to construct an extensive collection of mutants with missense mutations in the E5 gene. Characterization of mutants with amino acid substitutions in the hydrophobic middle third of the E5 protein indicated that efficient transformation requires a stretch of hydrophobic amino acids but not a specific amino acid sequence in this portion of the protein. Many amino acids in the carboxyl-terminal third of the protein can also undergo substitution without impairment of focus-forming activity, but the amino acids at seven positions, including two cysteine residues that mediate dimer formation, appear essential for efficient transforming activity. These essential amino acids are the most well conserved among related fibropapillomaviruses. The small size of the E5 protein, its lack of similarity to other transforming proteins, and its ability to tolerate many amino acid substitutions implies that it transforms cells via a novel mechanism.

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