Yj. Kim et al., CONTROL OF CELLULAR MORPHOGENESIS BY THE IPL2 BEM2 GTPASE-ACTIVATING PROTEIN - POSSIBLE ROLE OF PROTEIN-PHOSPHORYLATION, The Journal of cell biology, 127(5), 1994, pp. 1381-1394
The IPL2 gene is known to be required for normal polarized cell growth
in the budding yeast Saccharomyces cerevisiae. We now show that IPL2
is identical to the previously identified BEM2 gene. bem2 mutants are
defective in bud site selection at 26 degrees C and localized cell sur
face growth and organization of the actin cytoskeleton at 37 degrees C
. BEM2 encodes a protein with a COOH-terminal domain homologous to seq
uences found in several GTPase-activating proteins, including human Bc
r. The GTPase-activating protein-domain from the Bem2 protein (Bem2p)
or human Bcr can functionally substitute for Bem2p. The Rho1 and Rho2
GTPases are the likely in vivo targets of Bem2p because bem2 mutant ph
enotypes can be partially suppressed by increasing the gene dosage of
RHO1 or RHO2. CDC55 encodes the putative regulatory B subunit of prote
in phosphatase 2A, and mutations in BEM2 have previously been identifi
ed as suppressors of the cdc55-1 mutation. We show here that mutations
in the previously identified GRR1 gene can suppress bem2 mutations. g
rr1 and cdc55 mutants are both elongated in shape and cold-sensitive f
or growth, and cells lacking both GRR1 and CDC55 exhibit a synthetic l
ethal phenotype. bem2 mutant phenotypes also can be suppressed by the
SSD1-v1 (also known as SRK1) mutation, which was shown previously to s
uppress mutations in the protein phosphatase-encoding SIT4 gene. Cells
lacking both BEM2 and SIT4 exhibit a synthetic lethal phenotype even
in the presence of the SSD1-v1 suppressor. These genetic interactions
together suggest that protein phosphorylation and dephosphorylation pl
ay an important role in the BEM2-mediated process of polarized cell gr
owth.