TOR regulation of AGC kinases in yeast and mammals.

The TOR (target of rapamycin), an atypical protein kinase, is evolutionarily conserved from yeast to man. Pharmacological studies using rapamycin to inhibit TOR and yeast genetic studies have provided key insights on the function of TOR in growth regulation. One of the first bona fide cellular targets of TOR was the mammalian protein kinase p70 S6K (p70 S6 kinase), a member of a family of kinases called AGC (protein kinase A/protein kinase G/protein kinase C-family) kinases, which include PKA (cAMP-dependent protein kinase A), PKG (cGMP-dependent kinase) and PKC (protein kinase C).

KlROM2 encodes an essential GEF homologue in Kluyveromyces lactis.

Cellular integrity in yeasts is ensured by a rigid cell wall whose synthesis is controlled by a MAP kinase signal transduction cascade. In Saccharomyces cerevisiae upstream regulatory components of this MAP kinase pathway involve a single protein kinase C, which is regulated in part by interaction with the small GTPase Rho1p. This small G protein is in turn rendered inactive (GDP-bound) or is activated (GTP-bound) by the influence of GTPase activating proteins (GAPs) and the GDP/GTP exchange factors (GEFs), respectively.

Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control.

The target of rapamycin (TOR) proteins in Saccharomyces cerevisiae, TOR1 and TOR2, redundantly regulate growth in a rapamycin-sensitive manner. TOR2 additionally regulates polarization of the actin cytoskeleton in a rapamycin-insensitive manner. We describe two functionally distinct TOR complexes.

Rho5p downregulates the yeast cell integrity pathway.

The Rho family of proteins and their effectors are key regulators involved in many eukaryotic cell functions. In Saccharomyces cerevisiae the family consists of six members, Rho1p to Rho5p and Cdc42p. With the exception of Rho5p, these enzymes have been assigned different biological functions, including the regulation of polar growth, morphogenesis, actin cytoskeleton, budding and secretion.

Regulation of yeast protein kinase C activity by interaction with the small GTPase Rho1p through its amino-terminal HR1 domain.

Protein kinase C from Saccharomyces cerevisiae (Pkc1p) constitutes a prototypic member of the protein kinase C superfamily, as it shares all the conserved regions scattered among the isoenzymes of higher eukaryotes. The functional significance of some of the conserved domains in the yeast enzyme has not yet been investigated. We examined strains carrying a partial deletion in the amino-terminal region of the enzyme, which is homologous to the HR1 of the protein kinase C-related kinases.