c-Abl protein tyrosine kinase activity is tightly regulated in vertebr
ate cells. Several mutations, including deletions of the SH3 domain, c
an activate abl and convert it into an oncogene. To study c-Abl activi
ty in a cellular environment likely to lack specific regulators, we ha
ve expressed human c-Abl in Schizosaccharomyces pombe in an inducible
fashion. c-Abl, but not a kinase inactive form of the molecule, causes
growth arrest followed by death of the cells. Concomitant to Abl expr
ession we observed extensive phosphorylation of endogenous proteins on
tyrosine. Mutations in the SH2 domain or in the autophosphorylation s
ite dramatically reduce the ability of Abl to confer the growth arrest
phenotype and to phosphorylate endogenous proteins, suggesting a fund
amental role of these structures in the activity of the enzyme. An SH3
domain deletion mutant of Abl is equally active as wild type c-Abl in
yeast, even under conditions allowing detection of subtle differences
. These results demonstrate that there is no intrinsic regulation of c
-Abl kinase activity via the SH3 domain and suggest that the inhibitor
y effect of the SH3 domain observed in mammalian cells is mediated by
a factor that is absent in fission yeast. Expression of Abl in S.pombe
provides a novel quantitative assay for Abl activity and regulation.