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Crystal structures of free and ligand-bound focal adhesion targeting domain of Pyk2.

Lulo J, Yuzawa S, Schlessinger J
Biochem Biophys Res Commun 383 347-52 (2009)
Related entries: 3gm1, 3gm2

Cited: 26 times
EuropePMC logo PMID: 19358827

Abstract

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.

Reviews - 3gm3 mentioned but not cited (1)

  1. Identification and development of mPGES-1 inhibitors: where we are at? Chang HH, Meuillet EJ. Future Med Chem 3 1909-1934 (2011)

Articles - 3gm3 mentioned but not cited (4)

  1. Structural Basis for the Interaction between Pyk2-FAT Domain and Leupaxin LD Repeats. Vanarotti MS, Finkelstein DB, Guibao CD, Nourse A, Miller DJ, Zheng JJ. Biochemistry 55 1332-1345 (2016)
  2. Structural and mechanistic insights into the interaction between Pyk2 and paxillin LD motifs. Vanarotti MS, Miller DJ, Guibao CD, Nourse A, Zheng JJ. J Mol Biol 426 3985-4001 (2014)
  3. Comprehensive in silico Characterization of Universal Stress Proteins in Rice (Oryza sativa L.) With Insight Into Their Stress-Specific Transcriptional Modulation. Arabia S, Sami AA, Akhter S, Sarker RH, Islam T. Front Plant Sci 12 712607 (2021)
  4. The dipeptidyl peptidase IV inhibitors vildagliptin and K-579 inhibit a phospholipase C: a case of promiscuous scaffolds in proteins. Chakraborty S, Rendón-Ramírez A, Ásgeirsson B, Dutta M, Ghosh AS, Oda M, Venkatramani R, Rao BJ, Dandekar AM, Goñi FM. F1000Res 2 286 (2013)


Reviews citing this publication (7)

  1. FAK in cancer: mechanistic findings and clinical applications. Sulzmaier FJ, Jean C, Schlaepfer DD. Nat Rev Cancer 14 598-610 (2014)
  2. Focal adhesion kinase regulation of mechanotransduction and its impact on endothelial cell functions. Zebda N, Dubrovskyi O, Birukov KG. Microvasc Res 83 71-81 (2012)
  3. Targeting FAK in anticancer combination therapies. Dawson JC, Serrels A, Stupack DG, Schlaepfer DD, Frame MC. Nat Rev Cancer 21 313-324 (2021)
  4. Focal adhesion kinase (FAK) perspectives in mechanobiology: implications for cell behaviour. Tomakidi P, Schulz S, Proksch S, Weber W, Steinberg T. Cell Tissue Res 357 515-526 (2014)
  5. Endogenous Control Mechanisms of FAK and PYK2 and Their Relevance to Cancer Development. Naser R, Aldehaiman A, Díaz-Galicia E, Arold ST. Cancers (Basel) 10 E196 (2018)
  6. How to find a leucine in a haystack? Structure, ligand recognition and regulation of leucine-aspartic acid (LD) motifs. Alam T, Alazmi M, Gao X, Arold ST. Biochem J 460 317-329 (2014)
  7. The Non-receptor Tyrosine Kinase Pyk2 in Brain Function and Neurological and Psychiatric Diseases. de Pins B, Mendes T, Giralt A, Girault JA. Front Synaptic Neurosci 13 749001 (2021)

Articles citing this publication (14)

  1. FAK dimerization controls its kinase-dependent functions at focal adhesions. Brami-Cherrier K, Gervasi N, Arsenieva D, Walkiewicz K, Boutterin MC, Ortega A, Leonard PG, Seantier B, Gasmi L, Bouceba T, Kadaré G, Girault JA, Arold ST. EMBO J 33 356-370 (2014)
  2. Crystal structure of CCM3, a cerebral cavernous malformation protein critical for vascular integrity. Li X, Zhang R, Zhang H, He Y, Ji W, Min W, Boggon TJ. J Biol Chem 285 24099-24107 (2010)
  3. The direct effect of focal adhesion kinase (FAK), dominant-negative FAK, FAK-CD and FAK siRNA on gene expression and human MCF-7 breast cancer cell tumorigenesis. Golubovskaya VM, Zheng M, Zhang L, Li JL, Cance WG. BMC Cancer 9 280 (2009)
  4. CCM2-CCM3 interaction stabilizes their protein expression and permits endothelial network formation. Draheim KM, Li X, Zhang R, Fisher OS, Villari G, Boggon TJ, Calderwood DA. J Cell Biol 208 987-1001 (2015)
  5. Molecular recognition of leucine-aspartate repeat (LD) motifs by the focal adhesion targeting homology domain of cerebral cavernous malformation 3 (CCM3). Li X, Ji W, Zhang R, Folta-Stogniew E, Min W, Boggon TJ. J Biol Chem 286 26138-26147 (2011)
  6. NSP-Cas protein structures reveal a promiscuous interaction module in cell signaling. Mace PD, Wallez Y, Dobaczewska MK, Lee JJ, Robinson H, Pasquale EB, Riedl SJ. Nat Struct Mol Biol 18 1381-1387 (2011)
  7. Downregulation of FIP200 induces apoptosis of glioblastoma cells and microvascular endothelial cells by enhancing Pyk2 activity. Wang D, Olman MA, Stewart J, Tipps R, Huang P, Sanders PW, Toline E, Prayson RA, Lee J, Weil RJ, Palmer CA, Gillespie GY, Liu WM, Pieper RO, Guan JL, Gladson CL. PLoS One 6 e19629 (2011)
  8. A role for the protein tyrosine phosphatase CD45 in macrophage adhesion through the regulation of paxillin degradation. St-Pierre J, Ostergaard HL. PLoS One 8 e71531 (2013)
  9. A Novel Interaction between Pyk2 and MAP4K4 Is Integrated with Glioma Cell Migration. Loftus JC, Yang Z, Kloss J, Dhruv H, Tran NL, Riggs DL. J Signal Transduct 2013 956580 (2013)
  10. The Pyk2 FERM regulates Pyk2 complex formation and phosphorylation. Riggs D, Yang Z, Kloss J, Loftus JC. Cell Signal 23 288-296 (2011)
  11. Cooperative regulation of PBI1 and MAPKs controls WRKY45 transcription factor in rice immunity. Ichimaru K, Yamaguchi K, Harada K, Nishio Y, Hori M, Ishikawa K, Inoue H, Shigeta S, Inoue K, Shimada K, Yoshimura S, Takeda T, Yamashita E, Fujiwara T, Nakagawa A, Kojima C, Kawasaki T. Nat Commun 13 2397 (2022)
  12. The binding of DCC-P3 motif and FAK-FAT domain mediates the initial step of netrin-1/DCC signaling for axon attraction. Xu S, Liu Y, Li X, Liu Y, Meijers R, Zhang Y, Wang JH. Cell Discov 4 8 (2018)
  13. Hypophosphorylated and inactive Pyk2 associates with paxillin at the microtubule organizing center in hematopoietic cells. St-Pierre J, Lysechko TL, Ostergaard HL. Cell Signal 23 718-730 (2011)
  14. Structural basis of the target-binding mode of the G protein-coupled receptor kinase-interacting protein in the regulation of focal adhesion dynamics. Liang M, Xie X, Pan J, Jin G, Yu C, Wei Z. J Biol Chem 294 5827-5839 (2019)


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