MAP kinases as structural adaptors and enzymatic activators in transcription complexes

Abstract

Mitogen-activated protein kinase (MAPK) pathways regulate eukaryotic gene expression in response to extracellular stimuli. MAPKs and their downstream kinases phosphorylate transcription factors, co-regulators and chromatin proteins to initiate transcriptional changes. However, the spatial context in which the MAPKs operate in transcription complexes is poorly understood. Recent findings in budding yeast show that MAPKs can form integral components of transcription complexes and have novel structural functions in addition to phosphorylating local substrates. Hog1p MAPK is stably recruited to target promoters by specific transcription factors in response to osmotic stress, and acts as both a structural adaptor and enzymatic activator driving the assembly and activation of the transcription complex. We review the evidence that suggests a similar bifunctional role for MAPKs in mammalian transcription complexes.

MAPK cascades and major abiotic stresses

“…For example, the MAPKKK OMTK1 (oxidative stress-activated MAP triple kinase 1), which belongs to the alfalfa MAPKKK family, plays a role as an adapter and a phosphate transporter at the same time (Nakagami et al 2004). Other studies report that MAP kinases would act as structural adaptors and enzymatic activators in yeast (Edmunds and Mahadevan 2004). The presence of docking domains that form dovetail joints between compatible components in a given signaling pathway is another mechanism of MAP kinase specificity (Tanoue et al 2000).…”

The endoglycosidase heparanase enters the nucleus of T lymphocytes and modulates H3 methylation at actively transcribed genes via the interplay with key chromatin modifying enzymes

“…This finding is in accordance with previous studies that have shown that signal transduction kinases bind to the transcribed regions of target genes. 47,49,[51][52][53][54][55][56] Since heparanase is recruited to gene coding regions and associates with RNAP II, one may speculate that this enzyme may travel with the elongation complex through the coding regions of genes upon T cell activation. Indeed, such a mechanism has been proposed for yeast kinases that enter the coding regions of genes by "piggybacking" with RNAP II.…”

Oxidative stress-induced inhibition of adrenal steroidogenesis requires participation of p38 mitogen-activated protein kinase signaling pathway

“…Mitogen-activated protein kinase (MAPK) signal transduction pathways are well-characterized signaling networks that regulate a variety of cellular processes including gene transcription, protein synthesis, cell cycle, apoptosis, cell differentiation, inflammation, and cytoskeletal rearrangements (Lewis et al 1998, Widmann et al 1999, Kyriakis & Avruch 2001, Edmunds & Mahadevan 2004, Raman et al 2007, Whitmarsh 2007. MAPK signaling pathways can be triggered by a variety of stimuli including growth factors, cytokines, oxidative stress, environmental stress, and toxic chemical insults (Lewis et al 1998, Martindale & Holbrook 2002, Matsuzawa & Ichijo 2005, McCubrey et al 2006).…”