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A modeled hydrophobic domain on the TCL1 oncoprotein mediates association with AKT at the cytoplasmic membrane.

AKT has a critical role in relaying cell survival and proliferation signals initiated by ligand binding to surface receptors in mammalian cells. Induction of AKT serine/threonine kinase activity is augmented by the T-cell leukemia-1 (TCL1) oncoprotein through a physical association requiring the AKT pleckstrin homology domain. Here, we used molecular modeling and identified an exposed hydrophobic patch composed of two discontinuous amino acid stretches near one end of the TCL1 beta-barrel that was required for a TCL1-AKT association. Site-directed mutations of this region did not affect TCL1 secondary structure, yet they disrupted interactions with AKT. This region was found in other members of the TCL1 oncoprotein family, such as TCL1b and MTCP1, and suggested a conserved, novel AKT binding domain. Interestingly, TCL1 and AKT co-localize in multiple cell compartments, but only extracts from the plasma membrane stimulate optimal complex formation in vitro. Identification of an AKT binding domain on TCL1 is an important step in deciphering the complex interactions that regulate AKT kinase activity in lymphocyte development and neoplasia within the immune system.

Pubmed ID: 12009899


  • French SW
  • Shen RR
  • Koh PJ
  • Malone CS
  • Mallick P
  • Teitell MA



Publication Data

May 21, 2002

Associated Grants

  • Agency: NCI NIH HHS, Id: CA74929
  • Agency: NIGMS NIH HHS, Id: GM40185
  • Agency: NCI NIH HHS, Id: T32-CA09056

Mesh Terms

  • Animals
  • Cell Line
  • Cell Membrane
  • Cell Nucleus
  • Cytoplasm
  • DNA-Binding Proteins
  • Group II Phospholipases A2
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Intracellular Membranes
  • Jurkat Cells
  • Leukemia, T-Cell
  • Mice
  • Models, Molecular
  • Oncogene Proteins
  • Phospholipases A
  • Protein Biosynthesis
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-akt
  • Transcription Factors