Mixed - Lineage Protein kinases (MLKs) in inflammation, metabolism, and other disease states.
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.
Division of Cardiovascular Medicine, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, United States.
Siobhan M
SM
Craige
Division of Cardiovascular Medicine, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, United States.
Michaella M
MM
Reif
Division of Cardiovascular Medicine, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, United States. Electronic address: shashi.kant@umassmed.edu.
Shashi
S
Kant
D000818:Animals; D002318:Cardiovascular Diseases / Q000201:enzymology; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D007249:Inflammation / Q000201:enzymology*; D007333:Insulin Resistance / Q000502:physiology; D008107:Liver Diseases / Q000201:enzymology; D020930:MAP Kinase Kinase Kinases / Q000737:chemistry / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008659:Metabolic Diseases / Q000201:enzymology*; D024821:Metabolic Syndrome / Q000201:enzymology; D009369:Neoplasms / Q000201:enzymology; D009422:Nervous System Diseases / Q000201:enzymology; D009765:Obesity / Q000201:enzymology; D013312:Stress, Physiological
D016207:Cytokines; D020930:MAP Kinase Kinase Kinases
Disease; Inflammation; Insulin resistance; Kinase; Metabolism; Mixed-lineage kinase; Signal transduction