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Carboxyl-terminal modulator protein (CTMP), a negative regulator of PKB/Akt and v-Akt at the plasma membrane.

The PKB (protein kinase B, also called Akt) family of protein kinases plays a key role in insulin signaling, cellular survival, and transformation. PKB is activated by phosphorylation on residues threonine 308, by the protein kinase PDK1, and Serine 473, by a putative serine 473 kinase. Several protein binding partners for PKB have been identified. Here, we describe a protein partner for PKBalpha termed CTMP, or carboxyl-terminal modulator protein, that binds specifically to the carboxyl-terminal regulatory domain of PKBalpha at the plasma membrane. Binding of CTMP reduces the activity of PKBalpha by inhibiting phosphorylation on serine 473 and threonine 308. Moreover, CTMP expression reverts the phenotype of v-Akt-transformed cells examined under a number of criteria including cell morphology, growth rate, and in vivo tumorigenesis. These findings identify CTMP as a negative regulatory component of the pathway controlling PKB activity.

Pubmed ID: 11598301


  • Maira SM
  • Galetic I
  • Brazil DP
  • Kaech S
  • Ingley E
  • Thelen M
  • Hemmings BA


Science (New York, N.Y.)

Publication Data

October 12, 2001

Associated Grants


Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Carrier Proteins
  • Cell Division
  • Cell Line
  • Cell Line, Transformed
  • Cell Membrane
  • Cell Size
  • Enzyme Activation
  • Genes, fos
  • Humans
  • Insulin
  • Insulin-Like Growth Factor I
  • Membrane Proteins
  • Mice
  • Mice, Nude
  • Molecular Sequence Data
  • Neoplasms, Experimental
  • Oncogene Protein v-akt
  • Phosphorylation
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-akt
  • Recombinant Fusion Proteins
  • Retroviridae Proteins, Oncogenic
  • Signal Transduction
  • Thiolester Hydrolases
  • Transcription, Genetic
  • Transfection
  • Tumor Cells, Cultured
  • Vanadates