Role of the mixed-lineage protein kinase pathway in the metabolic stress response to obesity
Noh, Yun Hee
Jung, Dae Young
Kim, Jason K.
Davis, Roger J.
UMass Chan AffiliationsDepartment of Medicine, Division of Endocrinology, Metabolism and Diabetes
Program in Molecular Medicine
Document TypeJournal Article
JNK Mitogen-Activated Protein Kinases
MAP Kinase Kinase Kinases
Mice, Inbred C57BL
Cellular and Molecular Physiology
MetadataShow full item record
AbstractSaturated free fatty acid (FFA) is implicated in the metabolic response to obesity. In vitro studies indicate that FFA signaling may be mediated by the mixed-lineage protein kinase (MLK) pathway that activates cJun NH2-terminal kinase (JNK). Here, we examined the role of the MLK pathway in vivo using a mouse model of diet-induced obesity. The ubiquitously expressed MLK2 and MLK3 protein kinases have partially redundant functions. We therefore compared wild-type and compound mutant mice that lack expression of MLK2 and MLK3. MLK deficiency protected mice against high-fat-diet-induced insulin resistance and obesity. Reduced JNK activation and increased energy expenditure contribute to the metabolic effects of MLK deficiency. These data confirm that the MLK pathway plays a critical role in the metabolic response to obesity.
SourceKant S, Barrett T, Vertii A, Noh YH, Jung DY, Kim JK, Davis RJ. Role of the mixed-lineage protein kinase pathway in the metabolic stress response to obesity. Cell Rep. 2013 Aug 29;4(4):681-8. doi: 10.1016/j.celrep.2013.07.019. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/44395
Related ResourcesLink to Article in PubMed
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Role of the JIP4 scaffold protein in the regulation of mitogen-activated protein kinase signaling pathwaysKelkar, Nyaya; Standen, Claire L.; Davis, Roger J. (2005-03-16)The c-Jun NH2-terminal kinase (JNK)-interacting protein (JIP) group of scaffold proteins (JIP1, JIP2, and JIP3) can interact with components of the JNK signaling pathway and potently activate JNK. Here we describe the identification of a fourth member of the JIP family. The primary sequence of JIP4 is most closely related to that of JIP3. Like other members of the JIP family of scaffold proteins, JIP4 binds JNK and also the light chain of the microtubule motor protein kinesin-1. However, the function of JIP4 appears to be markedly different from other JIP proteins. Specifically, JIP4 does not activate JNK signaling. In contrast, JIP4 serves as an activator of the p38 mitogen-activated protein (MAP) kinase pathway by a mechanism that requires the MAP kinase kinases MKK3 and MKK6. The JIP4 scaffold protein therefore appears to be a new component of the p38 MAP kinase signaling pathway.
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