The stress-activated protein kinase pathways View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1999-08

AUTHORS

L. A. Tibbles, J. R. Woodgett

ABSTRACT

. Part of the cellular response to toxins, physical stresses and inflammatory cytokines occurs by signalling via the stress-activated protein kinase (SAPK) and p38 reactivating kinase pathways. This results in modification of cellular gene expression. These stress-responsive kinase pathways are structurally similar, but functionally distinct, from the archetypal mitogen-activated protein kinases (MAPKs or ERKs). The ERK pathway is a hierarchical cascade originating at the cell membrane with receptors for mitogens or growth factors, which recruit, via adapter proteins and exchange factors, the small guanosine triphosphatase (GTPase) Ras (see fig. 1). Ras activates raf, a serine threonine kinase, which activates MEK (MAPK/ERK kinase). MEK, in turn, phosphorylates and activates ERK1 and ERK2, which translocate to the nucleus and transactivate transcription factors, changing gene expression to promote growth, differentiation or mitosis. By transducing signals through a cascade of kinases, several options for control are introduced for amplifying and/or modifying the output signal. The SAPK and p38 pathways are also hierarchically arranged, but less is known about the upstream components and the downstream effects of stimulation of these pathways. Among the processes modulated by stress-responsive pathways are apoptosis, transformation, development, immune activation, inflammation and adaptation to environmental changes. This review outlines the upstream componentry of these pathways that interact with a variety of agonists to modify the activity of SAPK and p38, and explores the downstream functions of this activation. More... »

PAGES

1230-1254

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s000180050369

DOI

http://dx.doi.org/10.1007/s000180050369

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1030352707

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/10487205


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