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Cyclophilin A promotes cell migration via the Abl-Crk signaling pathway.

<div class='caption-title'>Binding between CypA and CrkII</div>
<div class='caption-title'>Specific interaction between CypA and CrkII in vitro and in vivo</div>
<div class='caption-title'>CypA attenuates CrkII Tyr221 phosphorylation in vitro and in vivo</div>
Saleh T, Jankowski W, Sriram G, Rossi P, Shah S, Lee KB, Cruz LA, Rodriguez AJ, Birge RB, Kalodimos CG
OpenAccess logo Nat Chem Biol 12 117-23 (2016)
Cited: 23 times
EuropePMC logo PMID: 26656091

Abstract

Cyclophilin A (CypA) is overexpressed in a number of human cancer types, but the mechanisms by which the protein promotes oncogenic properties of cells are not understood. Here we demonstrate that CypA binds the CrkII adaptor protein and prevents it from switching to the inhibited state. CrkII influences cell motility and invasion by mediating signaling through its SH2 and SH3 domains. CrkII Tyr221 phosphorylation by the Abl or EGFR kinases induces an inhibited state of CrkII by means of an intramolecular SH2-pTyr221 interaction, causing signaling interruption. We show that the CrkII phosphorylation site constitutes a binding site for CypA. Recruitment of CypA sterically restricts the accessibility of Tyr221 to kinases, thereby suppressing CrkII phosphorylation and promoting the active state. Structural, biophysical and in vivo data show that CypA augments CrkII-mediated signaling. A strong stimulation of cell migration is observed in cancer cells wherein both CypA and CrkII are greatly upregulated.

Articles - 2ms4 mentioned but not cited (2)

  1. Cyclophilin A promotes cell migration via the Abl-Crk signaling pathway. Saleh T, Jankowski W, Sriram G, Rossi P, Shah S, Lee KB, Cruz LA, Rodriguez AJ, Birge RB, Kalodimos CG. Nat Chem Biol 12 117-123 (2016)
  2. Cyclophilin A Inhibitor Debio-025 Targets Crk, Reduces Metastasis, and Induces Tumor Immunogenicity in Breast Cancer. Davra V, Saleh T, Geng K, Kimani S, Mehta D, Kasikara C, Smith B, Colangelo NW, Ciccarelli B, Li H, Azzam EI, Kalodimos CG, Birge RB, Kumar S. Mol Cancer Res 18 1189-1201 (2020)


Reviews citing this publication (4)

  1. Cyclophilin A: a key player for etiological agent infection. Liao Y, Luo D, Peng K, Zeng Y. Appl Microbiol Biotechnol 105 1365-1377 (2021)
  2. Application of small extracellular vesicles in the diagnosis and prognosis of nasopharyngeal carcinoma. Zhang J, Huang D, Lan X, Deng D, Li J, Zhang D, Li Y, Zhong T, Peng S. Front Cell Dev Biol 11 1100941 (2023)
  3. Inhibitors of Cyclophilin A: Current and Anticipated Pharmaceutical Agents for Inflammatory Diseases and Cancers. Zhao X, Zhao X, Di W, Wang C. Molecules 29 1235 (2024)
  4. Proline Isomerization: From the Chemistry and Biology to Therapeutic Opportunities. Gurung D, Danielson JA, Tasnim A, Zhang JT, Zou Y, Liu JY. Biology (Basel) 12 1008 (2023)

Articles citing this publication (17)

  1. A Slow Conformational Switch in the BMAL1 Transactivation Domain Modulates Circadian Rhythms. Gustafson CL, Parsley NC, Asimgil H, Lee HW, Ahlbach C, Michael AK, Xu H, Williams OL, Davis TL, Liu AC, Partch CL. Mol Cell 66 447-457.e7 (2017)
  2. Crk adaptor protein promotes PD-L1 expression, EMT and immune evasion in a murine model of triple-negative breast cancer. Kumar S, Davra V, Obr AE, Geng K, Wood TL, De Lorenzo MS, Birge RB. Oncoimmunology 7 e1376155 (2017)
  3. Exosomal cyclophilin A as a novel noninvasive biomarker for Epstein-Barr virus associated nasopharyngeal carcinoma. Liu L, Zuo L, Yang J, Xin S, Zhang J, Zhou J, Li G, Tang J, Lu J. Cancer Med 8 3142-3151 (2019)
  4. Ubiquitin-specific protease 4 promotes hepatocellular carcinoma progression via cyclophilin A stabilization and deubiquitination. Li T, Yan B, Ma Y, Weng J, Yang S, Zhao N, Wang X, Sun X. Cell Death Dis 9 148 (2018)
  5. A Proteomic Analysis of the Malignant Mesothelioma Secretome Using iTRAQ. Creaney J, Dick IM, Leon JS, Robinson BW. Cancer Genomics Proteomics 14 103-117 (2017)
  6. Composition of the Schistosoma mansoni worm secretome: Identification of immune modulatory Cyclophilin A. Floudas A, Cluxton CD, Fahel J, Khan AR, Saunders SP, Amu S, Alcami A, Fallon PG. PLoS Negl Trop Dis 11 e0006012 (2017)
  7. PEAK3/C19orf35 pseudokinase, a new NFK3 kinase family member, inhibits CrkII through dimerization. Lopez ML, Lo M, Kung JE, Dudkiewicz M, Jang GM, Von Dollen J, Johnson JR, Krogan NJ, Pawłowski K, Jura N. Proc Natl Acad Sci U S A 116 15495-15504 (2019)
  8. Cyclophilin A allows the allosteric regulation of a structural motif in the disordered domain 2 of NS5A and thereby fine-tunes HCV RNA replication. Dujardin M, Madan V, Gandhi NS, Cantrelle FX, Launay H, Huvent I, Bartenschlager R, Lippens G, Hanoulle X. J Biol Chem 294 13171-13185 (2019)
  9. One-pot synthesis of bioactive cyclopentenones from α-linolenic acid and docosahexaenoic acid. Maynard D, Müller SM, Hahmeier M, Löwe J, Feussner I, Gröger H, Viehhauser A, Dietz KJ. Bioorg Med Chem 26 1356-1364 (2018)
  10. MiR-378 modulates energy imbalance and apoptosis of mitochondria induced by doxorubicin. Wang Y, Zhang Q, Wei C, Zhao L, Guo X, Cui X, Shao L, Long J, Gu J, Zhao M. Am J Transl Res 10 3600-3609 (2018)
  11. Imatinib can act as an Allosteric Activator of Abl Kinase. Xie T, Saleh T, Rossi P, Miller D, Kalodimos CG. J Mol Biol 434 167349 (2022)
  12. Unfolding of CPR3 Gets Initiated at the Active Site and Proceeds via Two Intermediates. Shukla VK, Singh JS, Vispute N, Ahmad B, Kumar A, Hosur RV. Biophys J 112 605-619 (2017)
  13. Structural basis of interaction between dimeric cyclophilin 1 and Myb1 transcription factor in Trichomonas vaginalis. Martin T, Lou YC, Chou CC, Wei SY, Sadotra S, Cho CC, Lin MH, Tai JH, Hsu CH, Chen C. Sci Rep 8 5410 (2018)
  14. Cyclophilin A Controls Salmonella Internalization Levels and is Present at E. coli Actin-Rich Pedestals. Dhanda AS, Warren KE, Chiu RH, Guttman JA. Anat Rec (Hoboken) 301 2086-2094 (2018)
  15. Purification and characterization of Cyclophilin: a protein associated with protein folding in Salmonella Typhimurium. Kumawat M, Chaudhary D, Nabi B, Kumar M, Sarma DK, Shubham S, Karuna I, Ahlawat N, Ahlawat S. Arch Microbiol 203 5509-5517 (2021)
  16. Crosstalk between integrin/FAK and Crk/Vps25 governs invasion of bovine mammary epithelial cells by S. agalactiae. Guo Z, Ma Y, Jia Z, Wang L, Lu X, Chen Y, Wang Y, Hao H, Yu S, Wang Z. iScience 26 107884 (2023)
  17. [Expression of cyclophilin A in oral squamous cell carcinoma and its effect on cell proliferation and invasion]. Xia XY, Fang F, Liu Y, Che C, Ke JJ, Jiang SJ. Hua Xi Kou Qiang Yi Xue Za Zhi 39 164-169 (2021)


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