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PDBsum entry 1faq
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Serine/threonine protein kinase
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PDB id
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1faq
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References listed in PDB file
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Key reference
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Title
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The solution structure of the raf-1 cysteine-Rich domain: a novel ras and phospholipid binding site.
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Authors
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H.R.Mott,
J.W.Carpenter,
S.Zhong,
S.Ghosh,
R.M.Bell,
S.L.Campbell.
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Ref.
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Proc Natl Acad Sci U S A, 1996,
93,
8312-8317.
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PubMed id
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Abstract
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The Raf-1 protein kinase is the best-characterized downstream effector of
activated Ras. Interaction with Ras leads to Raf-1 activation and results in
transduction of cell growth and differentiation signals. The details of Raf-1
activation are unclear, but our characterization of a second Ras-binding site in
the cysteine-rich domain (CRD) and the involvement of both Ras-binding sites in
effective Raf-1-mediated transformation provides insight into the molecular
aspects and consequences of Ras-Raf interactions. The Raf-1 CRD is a member of
an emerging family of domains, many of which are found within signal transducing
proteins. Several contain binding sites for diacylglycerol (or phorbol esters)
and phosphatidylserine and are believed to play a role in membrane translocation
and enzyme activation. The CRD from Raf-1 does not bind diacylglycerol but
interacts with Ras and phosphatidylserine. To investigate the ligand-binding
specificities associated with CRDs, we have determined the solution structure of
the Raf-1 CRD using heteronuclear multidimensional NMR. We show that there are
differences between this structure and the structures of two related domains
from protein kinase C (PKC). The differences are confined to regions of the CRDs
involved in binding phorbol ester in the PKC domains. Since phosphatidylserine
is a common ligand, we expect its binding site to be located in regions where
the structures of the Raf-1 and PKC domains are similar. The structure of the
Raf-1 CRD represents an example of this family of domains that does not bind
diacylglycerol and provides a framework for investigating its interactions with
other molecules.
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