| Title: | Human ERK1 induces filamentous growth and cell wall remodeling pathways in Saccharomyces cerevisiae |
| Author(s): | Atienza JM; Suh M; Xenarios I; Landgraf R; Colicelli J; |
| Address: | "Department of Biological Chemistry and the Molecular Biology Institute, UCLA School of Medicine, Los Angeles, CA 90095, USA" |
| ISSN/ISBN: | 0021-9258 (Print) 0021-9258 (Linking) |
| Abstract: | "Expression of an activated extracellular signal-regulated kinase 1 (ERK1) construct in yeast cells was used to examine the conservation of function among mitogen-activated protein (MAP) kinases. Sequence alignment of the human MAP kinase ERK1 with all Saccharomyces cerevisiae kinases reveals a particularly strong kinship with Kss1p (invasive growth promoting MAP kinase), Fus3p (pheromone response MAP/ERK kinase), and Mpk1p (cell wall remodeling MAP kinase). A fusion protein of constitutively active human MAP/ERK kinase 1 (MEK) and human ERK1 was introduced under regulated expression into yeast cells. The fusion protein (MEK/ERK) induced a filamentation response element promoter and led to a growth retardation effect concomitant with a morphological change resulting in elongated cells, bipolar budding, and multicell chains. Induction of filamentous growth was also observed for diploid cells following MEK/ERK expression in liquid culture. Neither haploids nor diploids, however, showed marked penetration of agar medium. These effects could be triggered by either moderate MEK/ERK expression at 37 degrees C or by high level MEK/ERK expression at 30 degrees C. The combination of high level MEK/ERK expression and 37 degrees C resulted in cell death. The deleterious effects of MEK/ERK expression and high temperature were significantly mitigated by 1 m sorbitol, which also enhanced the filamentous phenotype. MEK/ERK was able to constitutively activate a cell wall maintenance reporter gene, suggesting misregulation of this pathway. In contrast, MEK/ERK effectively blocked expression from a pheromone-responsive element promoter and inhibited mating. These results are consistent with MEK/ERK promoting filamentous growth and altering the cell wall through its ability to partially mimic Kss1p and stimulate a pathway normally controlled by Mpk1p, while appearing to inhibit the normal functioning of the structurally related yeast MAP kinase Fus3p" |
| Keywords: | "Cell Division/*genetics Cell Wall/*metabolism Fungal Proteins/*metabolism Gene Expression Regulation, Enzymologic Gene Expression Regulation, Fungal Genes, Reporter Humans Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinases/*metabolism Ph;" |
| Notes: | "MedlineAtienza, J M Suh, M Xenarios, I Landgraf, R Colicelli, J eng NS31911/NS/NINDS NIH HHS/ Research Support, U.S. Gov't, P.H.S. 2000/04/29 J Biol Chem. 2000 Jul 7; 275(27):20638-46. doi: 10.1074/jbc.M910024199" |
