The rice blast fungus, Magnaporthe grisea, generates enormous turgor pressure within a specialized cell called the appressorium to breach the surface of host plant cells. Here, we show that a mitogen-activated protein kinase, Mps1, is essential for appressorium penetration. Mps1 is 85% similar to yeast Slt2 mitogen-activated protein kinase and can rescue the thermosensitive growth of slt2 null mutants. The mps1-1⌬ mutants of M. grisea have some phenotypes in common with slt2 mutants of yeast, including sensitivity to cell-wall-digesting enzymes, but display additional phenotypes, including reduced sporulation and fertility. Interestingly, mps1-1⌬ mutants are completely nonpathogenic because of the inability of appressoria to penetrate plant cell surfaces, suggesting that penetration requires remodeling of the appressorium wall through an Mps1-dependent signaling pathway. Although mps1-1⌬ mutants are unable to cause disease, they are able to trigger early plant-cell defense responses, including the accumulation of autofluorescent compounds and the rearrangement of the actin cytoskeleton. We conclude that MPS1 is essential for pathogen penetration; however, penetration is not required for induction of some plant defense responses.The plant cell wall provides such an effective barrier that many microorganisms can infect plants only through wounds or natural openings in the wall (1). A variety of fungal pathogens have evolved a complex morphogenetic program to sense specific components and properties of the plant cell surface and to differentiate specialized infectious cells, called appressoria, for penetrating the plant cell wall (2). Appressoria are produced by a wide range of taxonomically diverse fungal and nonfungal species (e.g., Oomycetes), suggesting that appressorium differentiation is a widespread microbial adaptation that assists in plant cell-wall penetration.The rice blast fungus, Magnaporthe grisea, infects most of the economically important cereal crops, particularly rice (3). Dispersed fungal spores (conidia) attach tightly to the plant surface, and under high moisture conditions, they germinate and differentiate a dome-shaped appressorium (4-6). The appressorium attaches tightly to the plant surface, and over several hours, turgor pressures within the appressorium reach 3-8 MPa, the highest measured turgor pressures for any cell (7,8). The fact that appressoria are capable of denting and penetrating inert hydrophobic surfaces (4) suggests that turgor pressure is the major force used to drive a thin penetration hypha through the plant cell wall.Turgor within the M. grisea appressorium is generated through a dramatic rise in intracellular glycerol levels (9). The efflux of glycerol from within the appressorium is prevented partially by a wall layer rich in polyketide-derived melanin.Mutations or chemicals that block the formation of the melanin wall layer allow the rapid efflux of glycerol, impair the maintenance of appressorium turgor, and prevent penetration (7, 9). Other cell-wall or membra...