title: The roles of MAPKs in disease.
abstract: MAP kinases transduce signals that are involved in a multitude of cellular pathways and functions in response to a variety of ligands and cell stimuli. Aberrant or inappropriate functions of MAPKs have now been identified in diseases ranging from cancer to inflammatory disease to obesity and diabetes. In many cell types, the MAPKs ERK1/2 are linked to cell proliferation. ERK1/2 are thought to play a role in some cancers, because mutations in Ras and B-Raf, which can activate the ERK1/2 cascade, are found in many human tumors. Abnormal ERK1/2 signaling has also been found in polycystic kidney disease, and serious developmental disorders such as cardio-facio-cutaneous syndrome arise from mutations in components of the ERK1/2 cascade. ERK1/2 are essential in well-differentiated cells and have been linked to long-term potentiation in neurons and in maintenance of epithelial polarity. Additionally, ERK1/2 are important for insulin gene transcription in pancreatic beta cells, which produce insulin in response to increases in circulating glucose to permit efficient glucose utilization and storage in the organism. Nutrients and hormones that induce or repress insulin secretion activate and/or inhibit ERK1/2 in a manner that reflects the secretory demand on beta cells. Disturbances in this and other regulatory pathways may result in the contribution of ERK1/2 to the etiology of certain human disorders.
authors.affiliation: Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park Road, Dallas, TX 75390-9041, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Lawrence
authors.forename: Arif
authors.initials: A
authors.lastname: Jivan
authors.forename: Chunli
authors.initials: C
authors.lastname: Shao
authors.forename: Lingling
authors.initials: L
authors.lastname: Duan
authors.forename: Daryl
authors.initials: D
authors.lastname: Goad
authors.forename: Elma
authors.initials: E
authors.lastname: Zaganjor
authors.forename: Jihan
authors.initials: J
authors.lastname: Osborne
authors.forename: Kathleen
authors.initials: K
authors.lastname: McGlynn
authors.forename: Steve
authors.initials: S
authors.lastname: Stippec
authors.forename: Svetlana
authors.initials: S
authors.lastname: Earnest
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Melanie H
authors.initials: MH
authors.lastname: Cobb
mesh_terms: D000818:Animals; D003920:Diabetes Mellitus / Q000201:enzymology; D004194:Disease; D006801:Humans; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009369:Neoplasms / Q000201:enzymology; D007690:Polycystic Kidney Diseases / Q000201:enzymology
chemical_list: D020928:Mitogen-Activated Protein Kinases