FISSION YEAST PAK1(-KINASE THAT INTERACTS WITH CDC42P AND IS INVOLVEDIN THE CONTROL OF CELL POLARITY AND MATING() ENCODES A PROTEIN)

A STE20/p65(pak) homolog was isolated from fission yeast by PCR. The p ak1(+) gene encodes a 72 kDa protein containing a putative p21-binding domain near its amino-terminus and a serine/threonine kinase domain n ear its carboxyl-terminus. The Pak1 protein autophosphorylates on seri ne residues and preferentially binds to activated Cdc42p both in vitro and in vivo, This binding is mediated through the p21 binding domain on Pak1p and the effector domain on Cdc42p. Overexpression of an inact ive mutant form of pak1 gives rise to cells with markedly abnormal sha pe with mislocalized actin staining, Pak1 overexpression does not, how ever, suppress lethality associated with cdc42-null cells or the morph ologic defect caused by overexpression of mutant cdc42 alleles, Gene d isruption of pak1+ establishes that, like cdc42(+), pak1(+) function i s required for cell viability, In budding yeast, pak1(+) expression re stores mating function to STE20-null cells and, in fission yeast, over expression of an inactive form of Pak inhibits mating. These results i ndicate that the Pak1 protein is likely to be an effector for Cdc42p o r a related GTPase, and suggest that Pak1p is involved in the maintena nce of cell polarity and in mating.