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(Received for publication, September 27, 1994; and in revised form, December 1,
1994) Deletion of the amino-terminal domain of Raf-1, which contains
the Ras-binding region, results in the constitutive activation of the
liberated Raf-1 catalytic domain in fibroblast cell lines. We
demonstrate that the MEK kinase activity of the isolated Raf-1
catalytic domain, Raf-BXB, is not constitutively active, but is
regulated in Jurkat T cells. Raf-BXB is activated by engaging the
antigen receptor-CD3 complex, or treating cells with phorbol myristate
acetate or okadaic acid. Increasing intracellular cAMP inhibits Raf-1
activation stimulated by phorbol myristate acetate, but not the
activation of Raf-BXB. Serine 621, but not serine 499, is essential for
Raf-BXB MEK kinase activity. Because Raf-BXB does not bind Ras, the
data establishes a Ras-independent signal in directly regulating the
activity of the Raf-1 catalytic domain.
Volume 270,
Number 10,
Issue of March 10, 1995 pp. 5594-5599
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
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