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PDBsum entry 2fo6
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Signaling protein,transferase
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PDB id
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2fo6
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References listed in PDB file
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Key reference
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Title
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Critical role of the ferm domain in pyk2 stimulated glioma cell migration.
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Authors
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C.A.Lipinski,
N.L.Tran,
A.Dooley,
Y.P.Pang,
C.Rohl,
J.Kloss,
Z.Yang,
W.Mcdonough,
D.Craig,
M.E.Berens,
J.C.Loftus.
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Ref.
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Biochem Biophys Res Commun, 2006,
349,
939-947.
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PubMed id
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Abstract
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The strong tendency of malignant glioma cells to invade locally into surrounding
normal brain precludes effective surgical resection, reduces the efficacy of
radiotherapy, and is associated with increased resistance to chemotherapy
regimens. We report that the N-terminal FERM domain of Pyk2 regulates its
promigratory function. A 3-dimensional model of the Pyk2 FERM domain was
generated and mutagenesis studies identified residues essential for Pyk2
promigratory function. Model-based targeted mutations within the FERM domain
decreased Pyk2 phosphorylation and reduced the capacity of Pyk2 to stimulate
glioma cell migration but did not significantly alter the intracellular
distribution of Pyk2. Expression of autonomous Pyk2 FERM domain fragments
containing analogous mutations exhibited reduced capacity to inhibit glioma cell
migration and Pyk2 phosphorylation relative to expression of an autonomous wild
type FERM domain fragment. These results indicate that the FERM domain plays an
important role in regulating the functional competency of Pyk2 as a promigratory
factor in glioma.
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