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Effect of C-terminal truncations on MLK7 catalytic activity and JNK activation

Xiaohong Yu1, Laura J Bloem

  • 1Cardiovascular Discovery Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA.

Biochemical and Biophysical Research Communications
|October 3, 2003
PubMed

Insights

Mixed lineage kinase 7 (MLK7) is crucial for activating JNK and p38 pathways. While the leucine zipper domain is important for full catalytic function, it is not essential for JNK activation by MLK7.

Area of Science:

  • Molecular biology
  • Cell signaling

Background:

  • Mixed lineage kinase 7 (MLK7) is a MAPKKK found in heart and skeletal muscle.
  • MLK7 activates JNK and p38 signaling pathways.
  • Conserved domains in MLKs, including a leucine zipper, are critical for catalytic activity and JNK activation.

Purpose of the Study:

  • To investigate the role of conserved domains in MLK7.
  • To determine the function of the leucine zipper domain in MLK7 catalytic activity and JNK activation.

Main Methods:

  • Generation of nested C-terminal deletion mutants of MLK7.
  • Generation of a MLK7 mutant lacking the leucine zipper (delLZ).
  • Assays to measure catalytic activity and JNK activation of MLK7 mutants.

Main Results:

  • The leucine zipper domain is required for full catalytic function of MLK7, but not absolutely essential.
  • MLK7 mutants MLK7(436) and delLZ showed full JNK activation.
  • MLK7 residues 322-436 are necessary for full pathway activation.

Conclusions:

  • The leucine zipper domain is not required for JNK activation by MLK7.
  • Specific C-terminal residues (322-436) are essential for maximal MLK7 pathway activation.

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