When expressed in yeast, mammalian mitogen-activated protein kinases lose proper regulation and become spontaneously phosphorylated

Vered Levin-Salomon, Inbai Maayan, Liat Avrahami-Moyal, Irit Marbach, Oded Livnah, David Engelberg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

MAPKs (mitogen-activated protein kinases) are key components in cell signalling pathways. Under optimal growth conditions, their activity is kept off, but in response to stimulation it is dramatically evoked. Because of the high degree of evolutionary conservation at the levels of sequence and mode of activation, MAPKs are believed to share similar regulatory mechanisms in all eukaryotes and to be functionally substitutable between them. To assess the reliability of this notion, we systematically analysed the activity, regulation and phenotypic effects of mammalian MAPKs in yeast. Unexpectedly, all mammalian MAPKs tested were spontaneously phosphorylated in yeast. JNKs (c-Jun N-terminal kinases) lost their phosphorylation in pbs2Δ cells, but p38s and ERKs (extracellular-signal-regulated kinases) maintained their spontaneous phosphorylation even in pbs2Δste7Δmkk1Δmkk2Δ cells. Kinase-dead variants of ERKs and p38s were phosphorylated in strains lacking a single MEK (MAPK/ERK kinase), but not in pbs2Δste7Δmkk1Δmkk2Δ cells. Thus, in yeast, p38 and ERKs are phosphorylated via a combined mechanism of autophosphorylation and MEK-mediated phosphorylation (any MEK).We further addressed the mechanism allowing mammalian MAPKs to exploit yeast MEKs in the absence of any activating signal.We suggest that mammalian MAPKs lost during evolution a C-terminal region that exists in some yeast MAPKs. Indeed, removal of this region from Hog1 and Mpk1 rendered them spontaneously and highly phosphorylated. It implies that MAPKs possess an efficient inherent autoposphorylation capability that is suppressed in yeast MAPKs via a C-terminal domain and in mammalian MAPKs via as yet unknown means.

Original languageAmerican English
Pages (from-to)331-340
Number of pages10
JournalBiochemical Journal
Volume417
Issue number1
DOIs
StatePublished - 1 Jan 2009

Keywords

  • Extracellular-signal-regulated kinase (ERK)
  • Mitogen-activated protein kinase (MAPK)
  • Phosphorylation
  • Yeast
  • c-Jun N-terminal kinase (JNK)
  • p38

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