Tissue distribution and functional expression of a cDNA encoding a novel mixed lineage kinase

Area of Science:

• Cardiovascular Biology
• Molecular Signaling
• Biochemistry

Background:

• Cardiac hypertrophy is an adaptive heart response to injury or overload, potentially leading to heart failure.
• The specific signaling pathways governing cardiac myocyte hypertrophy are not fully understood.

Purpose of the Study:

• To identify novel signaling molecules involved in cardiac hypertrophy using a human failed heart cDNA library.
• To characterize the function and signaling role of a newly identified kinase, MLK7.

Main Methods:

• Data mining of a human failed heart cDNA library to identify novel genes.
• Expression analysis of MLK7 mRNA in various tissues, focusing on cardiac myocytes.
• In vitro kinase activity assay of recombinant MLK7.
• Expression of MLK7 in cardiac myocytes to assess its effect on signaling pathways and cellular processes.

Main Results:

• A novel kinase, MLK7, belonging to the mixed lineage kinase (MLK) family, was identified.
• MLK7 exhibits serine/threonine kinase activity and is predominantly expressed in cardiac myocytes.
• Expression of MLK7 in cardiac myocytes activates stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and, to a lesser extent, ERK and p38 pathways.
• MLK7 induces fetal gene expression and increases protein synthesis in cardiac myocytes.

Conclusions:

• MLK7 is a novel member of the mixed lineage kinase family with a significant role in cardiac myocytes.
• MLK7 modulates the cardiac SAPK/JNK signaling pathway.
• MLK7 may play a critical role in the development and progression of cardiac hypertrophy and heart failure.