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J. Biol. Chem., Vol. 269, Issue 22, 15423-15426, Jun, 1994
M Abdellatif, WR MacLellan and MD Schneider
The molecular mechanisms for signaling by receptor serine/threonine kinases
are incompletely understood. To test the potential involvement of p21 H-Ras
proteins in signal transduction for type beta transforming growth factors
(TGF beta), TGF beta-responsive and constitutive reporter genes were
cotransfected into cardiac myocytes and mink lung epithelial cells, with
dominant inhibitory (Asn-17) or activated (Arg- 12) Ras expression vectors.
Asn-17 Ras inhibited both TGF beta- dependent and basal expression of
inducible promoters (skeletal alpha- actin and plasminogen activator
inhibitor-1), with equivalent dose- response relations. All seven reporter
constructs were comparably sensitive to down-regulation by Asn-17 Ras,
including those driven by nominally constitutive viral control regions or a
TATA-less initiator element. All constructs were up-regulated by Arg-12 Ras
more variably. Wild-type Ras had intermediate effects and could rescue a
minimal thymidine kinase promoter from inhibition by dominant negative Ras.
Thus, a Ras-dependent event is required for efficient expression of an
unexpectedly global or inclusive set of genes.
p21 Ras as a governor of global gene expression
Department of Medicine, Baylor College of Medicine, Houston, Texas 77030.
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