Mixed - Lineage Protein kinases (MLKs) in inflammation, metabolism, and other disease states

Biochim Biophys Acta. 2016 Sep;1862(9):1581-6. doi: 10.1016/j.bbadis.2016.05.022. Epub 2016 May 31.

Abstract

Mixed lineage kinases, or MLKs, are members of the MAP kinase kinase kinase (MAP3K) family, which were originally identified among the activators of the major stress-dependent mitogen activated protein kinases (MAPKs), JNK and p38. During stress, the activation of JNK and p38 kinases targets several essential downstream substrates that react in a specific manner to the unique stressor and thus determine the fate of the cell in response to a particular challenge. Recently, the MLK family was identified as a specific modulator of JNK and p38 signaling in metabolic syndrome. Moreover, the MLK family of kinases appears to be involved in a very wide spectrum of disorders. This review discusses the newly identified functions of MLKs in multiple diseases including metabolic disorders, inflammation, cancer, and neurological diseases.

Keywords: Disease; Inflammation; Insulin resistance; Kinase; Metabolism; Mixed-lineage kinase; Signal transduction.

Publication types

  • Review

MeSH terms

  • Animals
  • Cardiovascular Diseases / enzymology
  • Cytokines / biosynthesis
  • Humans
  • Inflammation / enzymology*
  • Insulin Resistance / physiology
  • Liver Diseases / enzymology
  • MAP Kinase Kinase Kinases / chemistry
  • MAP Kinase Kinase Kinases / metabolism*
  • MAP Kinase Signaling System
  • Metabolic Diseases / enzymology*
  • Metabolic Syndrome / enzymology
  • Neoplasms / enzymology
  • Nervous System Diseases / enzymology
  • Obesity / enzymology
  • Stress, Physiological

Substances

  • Cytokines
  • MAP Kinase Kinase Kinases