title: Wiring diagrams of MAPK regulation by MEKK1, 2, and 3.
abstract: Mitogen-activated protein kinase (MAPK) pathways are activated by a plethora of stimuli. The literature is filled with papers describing the activation of different MAPKs by almost any stimulus or insult imaginable to cells. In this review, we use signal transduction wiring diagrams to illustrate putative upstream regulators for the MAPK kinase kinases, MEKK1, 2, and 3. Targeted gene disruption of MEKK1, 2, or 3 defined phenotypes for each MEKK associated with loss of specific MAPK regulation. Genetic analysis of MEKK function clearly defines specific components of the wiring diagram that require MEKK1, 2, or 3 for physiological responses. We propose that signal transduction network wiring diagrams are valuable tools for hypothesis building and filtering physiologically relevant phenotypic responses from less connected protein relations in the regulation of MAPK pathways.
authors.affiliation: Department of Pharmacology, University of North Carolina School of Medicine, 1108 Mary Ellen Jones Building, CB# 7365, Chapel Hill, NC 27599, USA.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Uhlik
authors.forename: Amy N
authors.initials: AN
authors.lastname: Abell
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Cuevas
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nakamura
authors.forename: Gary L
authors.initials: GL
authors.lastname: Johnson
mesh_terms: D000818:Animals; D048728:MAP Kinase Kinase Kinase 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D048730:MAP Kinase Kinase Kinase 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D048748:MAP Kinase Kinase Kinase 3 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D051379:Mice; D018345:Mice, Knockout; D017434:Protein Structure, Tertiary
chemical_list: D048728:MAP Kinase Kinase Kinase 1; D048730:MAP Kinase Kinase Kinase 2; D048748:MAP Kinase Kinase Kinase 3