PDBsum entry 2fo6

Signaling protein,transferase

PDB id

2fo6

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Contents

			Protein chain

					306 a.a.

Theoretical model

PDB id:

2fo6

Links
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Name:

Signaling protein,transferase

Title:

3d model of a truncated human pyk2 ferm domain

Structure:

Protein tyrosine kinase 2 beta, ferm domain. Chain: x. Fragment: residues 45-350. Synonym: focal adhesion kinase 2. Fadk 2. Proline-rich tyrosine kinase 2. Cell adhesion kinase beta. Cak beta. Calcium-dependent tyrosine kinase. Cadtk. Related adhesion focal tyrosine kinase. Ec: 2.7.10.2

Source:

Homo sapiens. Human

Authors:

Y-P.Pang,A.J.Dooley

Key ref:

C.A.Lipinski et al. (2006). Critical role of the FERM domain in Pyk2 stimulated glioma cell migration. Biochem Biophys Res Commun, 349, 939-947. PubMed id: 16962067

Date:

12-Jan-06

Release date:

18-Apr-06

PROCHECK

	Headers

	References

Protein chain

Q14289 (FAK2_HUMAN) - Protein-tyrosine kinase 2-beta from Homo sapiens

Seq: Struc:

Seq: Struc:					1009 a.a. 306 a.a.

Key:

PfamA domain

Secondary structure

	Biochem Biophys Res Commun 349:939-947 (2006)
PubMed id: 16962067

Critical role of the FERM domain in Pyk2 stimulated glioma cell migration.
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.

ABSTRACT

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.

Literature references that cite this PDB file's key reference

PubMed id

Reference

20001213

C.A.Lipinski, and J.C.Loftus (2010).
Targeting Pyk2 for therapeutic intervention.

Expert Opin Ther Targets, 14, 95.

20966971

M.C.Frame, H.Patel, B.Serrels, D.Lietha, and M.J.Eck (2010).
The FERM domain: organizing the structure and function of FAK.

Nat Rev Mol Cell Biol, 11, 802-814.

19880522

S.T.Lim, N.L.Miller, J.O.Nam, X.L.Chen, Y.Lim, and D.D.Schlaepfer (2010).
Pyk2 inhibition of p53 as an adaptive and intrinsic mechanism facilitating cell proliferation and survival.

J Biol Chem, 285, 1743-1753.

18648907

C.A.Lipinski, N.L.Tran, C.Viso, J.Kloss, Z.Yang, M.E.Berens, and J.C.Loftus (2008).
Extended survival of Pyk2 or FAK deficient orthotopic glioma xenografts.

J Neurooncol, 90, 181-189.

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.