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New page: '''Unreleased structure''' The entry 3gm2 is ON HOLD Authors: Lulo, J.E., Yuzawa, S., Schlessinger, J. Description: Crystal Structure of the Focal Adhesion Targeting (FAT) Domain of Py...
 
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'''Unreleased structure'''


The entry 3gm2 is ON HOLD
==Crystal Structure of the Focal Adhesion Targeting (FAT) Domain of Pyk2==
<StructureSection load='3gm2' size='340' side='right'caption='[[3gm2]], [[Resolution|resolution]] 2.71&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3gm2]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GM2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GM2 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.71&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3gm2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gm2 OCA], [https://pdbe.org/3gm2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gm2 RCSB], [https://www.ebi.ac.uk/pdbsum/3gm2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gm2 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/FAK2_HUMAN FAK2_HUMAN] Note=Aberrant PTK2B/PYK2 expression may play a role in cancer cell proliferation, migration and invasion, in tumor formation and metastasis. Elevated PTK2B/PYK2 expression is seen in gliomas, hepatocellular carcinoma, lung cancer and breast cancer.<ref>PMID:18339875</ref> <ref>PMID:18765415</ref> <ref>PMID:19648005</ref> <ref>PMID:21533080</ref> <ref>PMID:20001213</ref> <ref>PMID:19428251</ref> <ref>PMID:19244237</ref>
== Function ==
[https://www.uniprot.org/uniprot/FAK2_HUMAN FAK2_HUMAN] Non-receptor protein-tyrosine kinase that regulates reorganization of the actin cytoskeleton, cell polarization, cell migration, adhesion, spreading and bone remodeling. Plays a role in the regulation of the humoral immune response, and is required for normal levels of marginal B-cells in the spleen and normal migration of splenic B-cells. Required for normal macrophage polarization and migration towards sites of inflammation. Regulates cytoskeleton rearrangement and cell spreading in T-cells, and contributes to the regulation of T-cell responses. Promotes osteoclastic bone resorption; this requires both PTK2B/PYK2 and SRC. May inhibit differentiation and activity of osteoprogenitor cells. Functions in signaling downstream of integrin and collagen receptors, immune receptors, G-protein coupled receptors (GPCR), cytokine, chemokine and growth factor receptors, and mediates responses to cellular stress. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and of the AKT1 signaling cascade. Promotes activation of NOS3. Regulates production of the cellular messenger cGMP. Promotes activation of the MAP kinase signaling cascade, including activation of MAPK1/ERK2, MAPK3/ERK1 and MAPK8/JNK1. Promotes activation of Rho family GTPases, such as RHOA and RAC1. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Acts as a scaffold, binding to both PDPK1 and SRC, thereby allowing SRC to phosphorylate PDPK1 at 'Tyr-9, 'Tyr-373', and 'Tyr-376'. Promotes phosphorylation of NMDA receptors by SRC family members, and thereby contributes to the regulation of NMDA receptor ion channel activity and intracellular Ca(2+) levels. May also regulate potassium ion transport by phosphorylation of potassium channel subunits. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ASAP1, NPHP1, KCNA2 and SHC1. Promotes phosphorylation of ASAP2, RHOU and PXN; this requires both SRC and PTK2/PYK2.<ref>PMID:7544443</ref> <ref>PMID:8849729</ref> <ref>PMID:8670418</ref> <ref>PMID:10022920</ref> <ref>PMID:12771146</ref> <ref>PMID:12893833</ref> <ref>PMID:14585963</ref> <ref>PMID:15050747</ref> <ref>PMID:15166227</ref> <ref>PMID:17634955</ref> <ref>PMID:18339875</ref> <ref>PMID:18765415</ref> <ref>PMID:18086875</ref> <ref>PMID:18587400</ref> <ref>PMID:19207108</ref> <ref>PMID:19648005</ref> <ref>PMID:19086031</ref> <ref>PMID:20521079</ref> <ref>PMID:19880522</ref> <ref>PMID:20381867</ref> <ref>PMID:21357692</ref> <ref>PMID:21533080</ref> <ref>PMID:20001213</ref> <ref>PMID:19428251</ref> <ref>PMID:19244237</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gm/3gm2_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3gm2 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Focal adhesion targeting (FAT) domains target the non-receptor tyrosine kinases FAK and Pyk2 to cellular focal adhesion areas, where the signaling molecule paxillin is also located. Here, we report the crystal structures of the Pyk2 FAT domain alone or in complex with paxillin LD4 peptides. The overall structure of Pyk2-FAT is an antiparallel four-helix bundle with an up-down, up-down, right-handed topology. In the LD4-bound FAT complex, two paxillin LD4 peptides interact with two opposite sides of Pyk2-FAT, at the surfaces of the alpha1alpha4 and alpha2alpha3 helices of each FAT molecule. We also demonstrate that, while paxillin is phosphorylated by Pyk2, complex formation between Pyk2 and paxillin does not depend on Pyk2 tyrosine kinase activity. These experiments reveal the structural basis underlying the selectivity of paxillin LD4 binding to the Pyk2 FAT domain and provide insights about the molecular details which influence the different behavior of these two closely-related kinases.


Authors: Lulo, J.E., Yuzawa, S., Schlessinger, J.
Crystal structures of free and ligand-bound focal adhesion targeting domain of Pyk2.,Lulo J, Yuzawa S, Schlessinger J Biochem Biophys Res Commun. 2009 Jun 5;383(3):347-52. Epub 2009 Apr 7. PMID:19358827<ref>PMID:19358827</ref>


Description: Crystal Structure of the Focal Adhesion Targeting (FAT) Domain of Pyk2
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3gm2" style="background-color:#fffaf0;"></div>


''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Mar 25 12:17:30 2009''
==See Also==
*[[Tyrosine kinase 3D structures|Tyrosine kinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Lulo JE]]
[[Category: Schlessinger J]]
[[Category: Yuzawa S]]

Latest revision as of 22:20, 29 May 2024

Crystal Structure of the Focal Adhesion Targeting (FAT) Domain of Pyk2Crystal Structure of the Focal Adhesion Targeting (FAT) Domain of Pyk2

Structural highlights

3gm2 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.71Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

FAK2_HUMAN Note=Aberrant PTK2B/PYK2 expression may play a role in cancer cell proliferation, migration and invasion, in tumor formation and metastasis. Elevated PTK2B/PYK2 expression is seen in gliomas, hepatocellular carcinoma, lung cancer and breast cancer.[1] [2] [3] [4] [5] [6] [7]

Function

FAK2_HUMAN Non-receptor protein-tyrosine kinase that regulates reorganization of the actin cytoskeleton, cell polarization, cell migration, adhesion, spreading and bone remodeling. Plays a role in the regulation of the humoral immune response, and is required for normal levels of marginal B-cells in the spleen and normal migration of splenic B-cells. Required for normal macrophage polarization and migration towards sites of inflammation. Regulates cytoskeleton rearrangement and cell spreading in T-cells, and contributes to the regulation of T-cell responses. Promotes osteoclastic bone resorption; this requires both PTK2B/PYK2 and SRC. May inhibit differentiation and activity of osteoprogenitor cells. Functions in signaling downstream of integrin and collagen receptors, immune receptors, G-protein coupled receptors (GPCR), cytokine, chemokine and growth factor receptors, and mediates responses to cellular stress. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and of the AKT1 signaling cascade. Promotes activation of NOS3. Regulates production of the cellular messenger cGMP. Promotes activation of the MAP kinase signaling cascade, including activation of MAPK1/ERK2, MAPK3/ERK1 and MAPK8/JNK1. Promotes activation of Rho family GTPases, such as RHOA and RAC1. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Acts as a scaffold, binding to both PDPK1 and SRC, thereby allowing SRC to phosphorylate PDPK1 at 'Tyr-9, 'Tyr-373', and 'Tyr-376'. Promotes phosphorylation of NMDA receptors by SRC family members, and thereby contributes to the regulation of NMDA receptor ion channel activity and intracellular Ca(2+) levels. May also regulate potassium ion transport by phosphorylation of potassium channel subunits. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ASAP1, NPHP1, KCNA2 and SHC1. Promotes phosphorylation of ASAP2, RHOU and PXN; this requires both SRC and PTK2/PYK2.[8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] [31] [32]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Focal adhesion targeting (FAT) domains target the non-receptor tyrosine kinases FAK and Pyk2 to cellular focal adhesion areas, where the signaling molecule paxillin is also located. Here, we report the crystal structures of the Pyk2 FAT domain alone or in complex with paxillin LD4 peptides. The overall structure of Pyk2-FAT is an antiparallel four-helix bundle with an up-down, up-down, right-handed topology. In the LD4-bound FAT complex, two paxillin LD4 peptides interact with two opposite sides of Pyk2-FAT, at the surfaces of the alpha1alpha4 and alpha2alpha3 helices of each FAT molecule. We also demonstrate that, while paxillin is phosphorylated by Pyk2, complex formation between Pyk2 and paxillin does not depend on Pyk2 tyrosine kinase activity. These experiments reveal the structural basis underlying the selectivity of paxillin LD4 binding to the Pyk2 FAT domain and provide insights about the molecular details which influence the different behavior of these two closely-related kinases.

Crystal structures of free and ligand-bound focal adhesion targeting domain of Pyk2.,Lulo J, Yuzawa S, Schlessinger J Biochem Biophys Res Commun. 2009 Jun 5;383(3):347-52. Epub 2009 Apr 7. PMID:19358827[33]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Roberts WG, Ung E, Whalen P, Cooper B, Hulford C, Autry C, Richter D, Emerson E, Lin J, Kath J, Coleman K, Yao L, Martinez-Alsina L, Lorenzen M, Berliner M, Luzzio M, Patel N, Schmitt E, LaGreca S, Jani J, Wessel M, Marr E, Griffor M, Vajdos F. Antitumor activity and pharmacology of a selective focal adhesion kinase inhibitor, PF-562,271. Cancer Res. 2008 Mar 15;68(6):1935-44. PMID:18339875 doi:68/6/1935
  2. ↑ Sun CK, Man K, Ng KT, Ho JW, Lim ZX, Cheng Q, Lo CM, Poon RT, Fan ST. Proline-rich tyrosine kinase 2 (Pyk2) promotes proliferation and invasiveness of hepatocellular carcinoma cells through c-Src/ERK activation. Carcinogenesis. 2008 Nov;29(11):2096-105. doi: 10.1093/carcin/bgn203. Epub 2008, Sep 1. PMID:18765415 doi:10.1093/carcin/bgn203
  3. ↑ Allen JG, Lee MR, Han CY, Scherrer J, Flynn S, Boucher C, Zhao H, O'Connor AB, Roveto P, Bauer D, Graceffa R, Richards WG, Babij P. Identification of small molecule inhibitors of proline-rich tyrosine kinase 2 (Pyk2) with osteogenic activity in osteoblast cells. Bioorg Med Chem Lett. 2009 Sep 1;19(17):4924-8. doi: 10.1016/j.bmcl.2009.07.084. , Epub 2009 Jul 22. PMID:19648005 doi:10.1016/j.bmcl.2009.07.084
  4. ↑ Sun CK, Ng KT, Lim ZX, Cheng Q, Lo CM, Poon RT, Man K, Wong N, Fan ST. Proline-rich tyrosine kinase 2 (Pyk2) promotes cell motility of hepatocellular carcinoma through induction of epithelial to mesenchymal transition. PLoS One. 2011 Apr 20;6(4):e18878. doi: 10.1371/journal.pone.0018878. PMID:21533080 doi:10.1371/journal.pone.0018878
  5. ↑ Lipinski CA, Loftus JC. Targeting Pyk2 for therapeutic intervention. Expert Opin Ther Targets. 2010 Jan;14(1):95-108. doi: 10.1517/14728220903473194. PMID:20001213 doi:10.1517/14728220903473194
  6. ↑ Walker DP, Zawistoski MP, McGlynn MA, Li JC, Kung DW, Bonnette PC, Baumann A, Buckbinder L, Houser JA, Boer J, Mistry A, Han S, Xing L, Guzman-Perez A. Sulfoximine-substituted trifluoromethylpyrimidine analogs as inhibitors of proline-rich tyrosine kinase 2 (PYK2) show reduced hERG activity. Bioorg Med Chem Lett. 2009 Jun 15;19(12):3253-8. Epub 2009 Apr 24. PMID:19428251 doi:10.1016/j.bmcl.2009.04.093
  7. ↑ Han S, Mistry A, Chang JS, Cunningham D, Griffor M, Bonnette PC, Wang H, Chrunyk BA, Aspnes GE, Walker DP, Brosius AD, Buckbinder L. Structural characterization of proline-rich tyrosine kinase 2 (PYK2) reveals a unique (DFG-out) conformation and enables inhibitor design. J Biol Chem. 2009 May 8;284(19):13193-201. Epub 2009 Feb 25. PMID:19244237 doi:10.1074/jbc.M809038200
  8. ↑ Lev S, Moreno H, Martinez R, Canoll P, Peles E, Musacchio JM, Plowman GD, Rudy B, Schlessinger J. Protein tyrosine kinase PYK2 involved in Ca(2+)-induced regulation of ion channel and MAP kinase functions. Nature. 1995 Aug 31;376(6543):737-45. PMID:7544443 doi:http://dx.doi.org/10.1038/376737a0
  9. ↑ Dikic I, Tokiwa G, Lev S, Courtneidge SA, Schlessinger J. A role for Pyk2 and Src in linking G-protein-coupled receptors with MAP kinase activation. Nature. 1996 Oct 10;383(6600):547-50. PMID:8849729 doi:10.1038/383547a0
  10. ↑ Tokiwa G, Dikic I, Lev S, Schlessinger J. Activation of Pyk2 by stress signals and coupling with JNK signaling pathway. Science. 1996 Aug 9;273(5276):792-4. PMID:8670418
  11. ↑ Andreev J, Simon JP, Sabatini DD, Kam J, Plowman G, Randazzo PA, Schlessinger J. Identification of a new Pyk2 target protein with Arf-GAP activity. Mol Cell Biol. 1999 Mar;19(3):2338-50. PMID:10022920
  12. ↑ Kruljac-Letunic A, Moelleken J, Kallin A, Wieland F, Blaukat A. The tyrosine kinase Pyk2 regulates Arf1 activity by phosphorylation and inhibition of the Arf-GTPase-activating protein ASAP1. J Biol Chem. 2003 Aug 8;278(32):29560-70. Epub 2003 May 27. PMID:12771146 doi:10.1074/jbc.M302278200
  13. ↑ Takahashi T, Yamashita H, Nagano Y, Nakamura T, Ohmori H, Avraham H, Avraham S, Yasuda M, Matsumoto M. Identification and characterization of a novel Pyk2/related adhesion focal tyrosine kinase-associated protein that inhibits alpha-synuclein phosphorylation. J Biol Chem. 2003 Oct 24;278(43):42225-33. Epub 2003 Jul 31. PMID:12893833 doi:10.1074/jbc.M213217200
  14. ↑ Taniyama Y, Weber DS, Rocic P, Hilenski L, Akers ML, Park J, Hemmings BA, Alexander RW, Griendling KK. Pyk2- and Src-dependent tyrosine phosphorylation of PDK1 regulates focal adhesions. Mol Cell Biol. 2003 Nov;23(22):8019-29. PMID:14585963
  15. ↑ Dylla SJ, Deyle DR, Theunissen K, Padurean AM, Verfaillie CM. Integrin engagement-induced inhibition of human myelopoiesis is mediated by proline-rich tyrosine kinase 2 gene products. Exp Hematol. 2004 Apr;32(4):365-74. PMID:15050747 doi:10.1016/j.exphem.2004.01.001
  16. ↑ Park SY, Avraham HK, Avraham S. RAFTK/Pyk2 activation is mediated by trans-acting autophosphorylation in a Src-independent manner. J Biol Chem. 2004 Aug 6;279(32):33315-22. Epub 2004 May 27. PMID:15166227 doi:10.1074/jbc.M313527200
  17. ↑ Hjorthaug HS, Aasheim HC. Ephrin-A1 stimulates migration of CD8+CCR7+ T lymphocytes. Eur J Immunol. 2007 Aug;37(8):2326-36. PMID:17634955 doi:10.1002/eji.200737111
  18. ↑ Roberts WG, Ung E, Whalen P, Cooper B, Hulford C, Autry C, Richter D, Emerson E, Lin J, Kath J, Coleman K, Yao L, Martinez-Alsina L, Lorenzen M, Berliner M, Luzzio M, Patel N, Schmitt E, LaGreca S, Jani J, Wessel M, Marr E, Griffor M, Vajdos F. Antitumor activity and pharmacology of a selective focal adhesion kinase inhibitor, PF-562,271. Cancer Res. 2008 Mar 15;68(6):1935-44. PMID:18339875 doi:68/6/1935
  19. ↑ Sun CK, Man K, Ng KT, Ho JW, Lim ZX, Cheng Q, Lo CM, Poon RT, Fan ST. Proline-rich tyrosine kinase 2 (Pyk2) promotes proliferation and invasiveness of hepatocellular carcinoma cells through c-Src/ERK activation. Carcinogenesis. 2008 Nov;29(11):2096-105. doi: 10.1093/carcin/bgn203. Epub 2008, Sep 1. PMID:18765415 doi:10.1093/carcin/bgn203
  20. ↑ Ruusala A, Aspenstrom P. The atypical Rho GTPase Wrch1 collaborates with the nonreceptor tyrosine kinases Pyk2 and Src in regulating cytoskeletal dynamics. Mol Cell Biol. 2008 Mar;28(5):1802-14. Epub 2007 Dec 17. PMID:18086875 doi:10.1128/MCB.00201-07
  21. ↑ Xu J, Gao XP, Ramchandran R, Zhao YY, Vogel SM, Malik AB. Nonmuscle myosin light-chain kinase mediates neutrophil transmigration in sepsis-induced lung inflammation by activating beta2 integrins. Nat Immunol. 2008 Aug;9(8):880-6. doi: 10.1038/ni.1628. Epub 2008 Jun 29. PMID:18587400 doi:10.1038/ni.1628
  22. ↑ Gao C, Blystone SD. A Pyk2-Vav1 complex is recruited to beta3-adhesion sites to initiate Rho activation. Biochem J. 2009 Apr 28;420(1):49-56. doi: 10.1042/BJ20090037. PMID:19207108 doi:10.1042/BJ20090037
  23. ↑ Allen JG, Lee MR, Han CY, Scherrer J, Flynn S, Boucher C, Zhao H, O'Connor AB, Roveto P, Bauer D, Graceffa R, Richards WG, Babij P. Identification of small molecule inhibitors of proline-rich tyrosine kinase 2 (Pyk2) with osteogenic activity in osteoblast cells. Bioorg Med Chem Lett. 2009 Sep 1;19(17):4924-8. doi: 10.1016/j.bmcl.2009.07.084. , Epub 2009 Jul 22. PMID:19648005 doi:10.1016/j.bmcl.2009.07.084
  24. ↑ Rufanova VA, Alexanian A, Wakatsuki T, Lerner A, Sorokin A. Pyk2 mediates endothelin-1 signaling via p130Cas/BCAR3 cascade and regulates human glomerular mesangial cell adhesion and spreading. J Cell Physiol. 2009 Apr;219(1):45-56. doi: 10.1002/jcp.21649. PMID:19086031 doi:10.1002/jcp.21649
  25. ↑ Shen X, Xi G, Radhakrishnan Y, Clemmons DR. Recruitment of Pyk2 to SHPS-1 signaling complex is required for IGF-I-dependent mitogenic signaling in vascular smooth muscle cells. Cell Mol Life Sci. 2010 Nov;67(22):3893-903. doi: 10.1007/s00018-010-0411-x. Epub, 2010 Jun 3. PMID:20521079 doi:10.1007/s00018-010-0411-x
  26. ↑ Lim ST, Miller NL, Nam JO, Chen XL, Lim Y, Schlaepfer DD. Pyk2 inhibition of p53 as an adaptive and intrinsic mechanism facilitating cell proliferation and survival. J Biol Chem. 2010 Jan 15;285(3):1743-53. doi: 10.1074/jbc.M109.064212. Epub 2009 , Oct 30. PMID:19880522 doi:10.1074/jbc.M109.064212
  27. ↑ Collins M, Bartelt RR, Houtman JC. T cell receptor activation leads to two distinct phases of Pyk2 activation and actin cytoskeletal rearrangement in human T cells. Mol Immunol. 2010 May;47(9):1665-74. doi: 10.1016/j.molimm.2010.03.009. Epub 2010, Apr 9. PMID:20381867 doi:10.1016/j.molimm.2010.03.009
  28. ↑ Liebau MC, Hopker K, Muller RU, Schmedding I, Zank S, Schairer B, Fabretti F, Hohne M, Bartram MP, Dafinger C, Hackl M, Burst V, Habbig S, Zentgraf H, Blaukat A, Walz G, Benzing T, Schermer B. Nephrocystin-4 regulates Pyk2-induced tyrosine phosphorylation of nephrocystin-1 to control targeting to monocilia. J Biol Chem. 2011 Apr 22;286(16):14237-45. doi: 10.1074/jbc.M110.165464. Epub, 2011 Feb 28. PMID:21357692 doi:10.1074/jbc.M110.165464
  29. ↑ Sun CK, Ng KT, Lim ZX, Cheng Q, Lo CM, Poon RT, Man K, Wong N, Fan ST. Proline-rich tyrosine kinase 2 (Pyk2) promotes cell motility of hepatocellular carcinoma through induction of epithelial to mesenchymal transition. PLoS One. 2011 Apr 20;6(4):e18878. doi: 10.1371/journal.pone.0018878. PMID:21533080 doi:10.1371/journal.pone.0018878
  30. ↑ Lipinski CA, Loftus JC. Targeting Pyk2 for therapeutic intervention. Expert Opin Ther Targets. 2010 Jan;14(1):95-108. doi: 10.1517/14728220903473194. PMID:20001213 doi:10.1517/14728220903473194
  31. ↑ Walker DP, Zawistoski MP, McGlynn MA, Li JC, Kung DW, Bonnette PC, Baumann A, Buckbinder L, Houser JA, Boer J, Mistry A, Han S, Xing L, Guzman-Perez A. Sulfoximine-substituted trifluoromethylpyrimidine analogs as inhibitors of proline-rich tyrosine kinase 2 (PYK2) show reduced hERG activity. Bioorg Med Chem Lett. 2009 Jun 15;19(12):3253-8. Epub 2009 Apr 24. PMID:19428251 doi:10.1016/j.bmcl.2009.04.093
  32. ↑ Han S, Mistry A, Chang JS, Cunningham D, Griffor M, Bonnette PC, Wang H, Chrunyk BA, Aspnes GE, Walker DP, Brosius AD, Buckbinder L. Structural characterization of proline-rich tyrosine kinase 2 (PYK2) reveals a unique (DFG-out) conformation and enables inhibitor design. J Biol Chem. 2009 May 8;284(19):13193-201. Epub 2009 Feb 25. PMID:19244237 doi:10.1074/jbc.M809038200
  33. ↑ Lulo J, Yuzawa S, Schlessinger J. Crystal structures of free and ligand-bound focal adhesion targeting domain of Pyk2. Biochem Biophys Res Commun. 2009 Jun 5;383(3):347-52. Epub 2009 Apr 7. PMID:19358827 doi:10.1016/j.bbrc.2009.04.011

3gm2, resolution 2.71Å

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