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J. Cell Biol.,
Volume 143, Number 2, October 19, 1998 375-389
Department of Biochemistry and Biophysics, University of California, San Francisco, California 94143-0448
We showed previously that protein kinase C,
which is required to maintain cell integrity, negatively
regulates cell fusion (Philips, J., and I. Herskowitz.
1997. J. Cell Biol. 138:961-974). To identify additional
genes involved in cell fusion, we looked for genes
whose overexpression relieved the defect caused by activated alleles of Pkc1p. This strategy led to the identification of a novel gene, KEL1, which encodes a protein
composed of two domains, one containing six kelch repeats, a motif initially described in the Drosophila protein Kelch (Xue, F., and L. Cooley. 1993. Cell. 72:681-
693), and another domain predicted to form coiled coils. Overexpression of KEL1 also suppressed the defect in cell fusion of spa2
and fps1
mutants. KEL2,
which corresponds to ORF YGR238c, encodes a protein highly similar to Kel1p. Its overexpression also
suppressed the mating defect associated with activated
Pkc1p. Mutants lacking KEL1 exhibited a moderate
defect in cell fusion that was exacerbated by activated
alleles of Pkc1p or loss of FUS1, FUS2, or FPS1, but
not by loss of SPA2. kel1
mutants form cells that are
elongated and heterogeneous in shape, indicating that
Kel1p is also required for proper morphology during
vegetative growth. In contrast, kel2
mutants were not
impaired in cell fusion or morphology. Both Kel1p and
Kel2p localized to the site where cell fusion occurs during mating and to regions of polarized growth during
vegetative growth. Coimmunoprecipitation and two-hybrid analyses indicated that Kel1p and Kel2p physically interact. We conclude that Kel1p has a role in cell
morphogenesis and cell fusion and may antagonize the
Pkc1p pathway.
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