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Vol. 9, Issue 8, 2231-2247, August 1998
Department of Cell Biology and Anatomy, The Johns Hopkins
University School of Medicine, Baltimore, Maryland 21205
Eukaryotic proteins containing a C-terminal CAAX motif undergo a
series of posttranslational CAAX-processing events that include isoprenylation, C-terminal proteolytic cleavage, and carboxyl methylation. We demonstrated previously that the STE14
gene product of Saccharomyces cerevisiae mediates the
carboxyl methylation step of CAAX processing in yeast. In this study,
we have investigated the subcellular localization of Ste14p, a
predicted membrane-spanning protein, using a polyclonal antibody
generated against the C terminus of Ste14p and an in vitro
methyltransferase assay. We demonstrate by immunofluorescence and
subcellular fractionation that Ste14p and its associated activity are
localized to the endoplasmic reticulum (ER) membrane of yeast. In
addition, other studies from our laboratory have shown that the CAAX
proteases are also ER membrane proteins. Together these results
indicate that the intracellular site of CAAX protein processing is the
ER membrane, presumably on its cytosolic face. Interestingly, the
insertion of a hemagglutinin epitope tag at the N terminus, at the C
terminus, or at an internal site disrupts the ER localization of Ste14p
and results in its mislocalization, apparently to the Golgi. We have
also expressed the Ste14p homologue from Schizosaccharomyces
pombe, mam4p, in S. cerevisiae and have shown
that mam4p complements a 
ste14 mutant. This finding,
plus additional recent examples of cross-species complementation,
indicates that the CAAX methyltransferase family consists of functional
homologues.
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