MEKK2 regulates paxillin ubiquitylation and localization in MDA-MB 231 breast cancer cells

被引:11
|
作者
Ameka, Magdalene [1 ]
Kahle, Michael P. [1 ]
Perez-Neut, Mathew [1 ]
Gentile, Saverio [1 ]
Mirza, Ahmed A. [1 ]
Cuevas, Bruce D. [1 ]
机构
[1] Loyola Univ Chicago, Stritch Sch Med, Dept Mol Pharmacol & Therapeut, Maywood, IL 60153 USA
基金
美国国家卫生研究院;
关键词
fibronectin; focal adhesion; kinase; MEKK2; paxillin; ubiquitylation; TYROSINE PHOSPHORYLATION; GROWTH-FACTOR; MIGRATION; ADHESION; KINASE; PROTEIN; BINDING; MLK3; ASSOCIATION; DISRUPTION;
D O I
10.1042/BJ20140420
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The intracellular kinase MEKK2 (mitogen-activated protein kinase/extracellular-signal-regulated kinase kinase kinase 2) is an upstream regulator of JNK (c-Jun N-terminal kinase), but additional functions for MEKK2 have not been well defined. Silencing MEKK2 expression in invasive breast tumour cells markedly inhibits xenograft metastasis, indicating that MEKK2 controls tumour cell function required for tumour progression. In our previous investigation of MEKK2 function, we discovered that tumour cell attachment to fibronectin recruits MEKK2 to focal adhesion complexes, and that MEKK2 knockdown is associated with stabilized focal adhesions and significant inhibition of tumour cell migration. In the present study we investigate MEKK2 function in focal adhesions and we report that MEKK2 physically associates with the LD1 motif of the focal adhesion protein paxillin. We reveal that MEKK2 induces paxillin ubiquitylation, and that this function requires both the paxillin LD1 motif and MEKK2 kinase activity. Finally, we demonstrate that MEKK2 promotes paxillin redistribution from focal adhesions into the cytoplasm, but does not promote paxillin degradation. Taken together, our results reveal a novel function for MEKK2 as a regulator of ubiquitylation-dependent paxillin redistribution in breast tumour cells.
引用
收藏
页码:99 / 108
页数:10
相关论文
共 50 条
  • [1] MEKK2 regulates focal adhesion stability and motility in invasive breast cancer cells
    Mirza, Ahmed A.
    Kahle, Michael P.
    Ameka, Magdalene
    Campbell, Edward M.
    Cuevas, Bruce D.
    BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2014, 1843 (05): : 945 - 954
  • [2] ARF1 regulates adhesion of MDA-MB-231 invasive breast cancer cells through formation of focal adhesions
    Schlienger, Sabrina
    Ramirez, Rodrigo Alain Migueles
    Claing, Audrey
    CELLULAR SIGNALLING, 2015, 27 (03) : 403 - 415
  • [3] Effect of p27 on motility of MDA-MB-231 breast cancer cells
    Lee, Eun Young
    Jeon, Min Jeong
    Yang, Wonseok
    Shin, Incheol
    ONCOLOGY REPORTS, 2009, 21 (06) : 1621 - 1625
  • [4] Anti-Cancer Effects of Sulfasalazine and Vitamin E Succinate in MDA-MB 231 Triple-Negative Breast Cancer Cells
    Wei, Chyou-Wei
    Yu, Yung-Luen
    Lu, Ji-Ying
    Hung, Yu-Ting
    Liu, Hsiao-Chun
    Yiang, Giou-Teng
    INTERNATIONAL JOURNAL OF MEDICAL SCIENCES, 2019, 16 (04): : 494 - 500
  • [5] Hesperetin Inhibits TGF-β1-Induced Migration and Invasion of Triple Negative Breast Cancer MDA-MB-231 Cells via Suppressing Fyn/Paxillin/RhoA Pathway
    Lu, Qian
    Lai, Yongwei
    Zhang, Hong
    Ren, Kuang
    Liu, Wei
    An, Ying
    Yao, Jiahong
    Fan, Hongyan
    INTEGRATIVE CANCER THERAPIES, 2022, 21
  • [6] Synthesis of potent MDA-MB 231 breast cancer drug molecules from single step
    Govindaraj, Senthilnathan
    Ganesan, Kilivelu
    Dharmasivam, Mahendiran
    Raman, Lakshmisundaram
    Alam, Mohammed Mujahid
    Amanullah, Mohammed
    SCIENTIFIC REPORTS, 2023, 13 (01)
  • [7] The Triple-negative Breast Cancer Cell Line MDA-MB 231 Is Specifically Inhibited by the Ionophore Salinomycin
    Hero, Thomas
    Buehler, Helmut
    Kouam, Pascaline Nguemgo
    Priesch-Grzeszowiak, Bettina
    Lateit, Tatiana
    Adamietz, Irenaus Anton
    ANTICANCER RESEARCH, 2019, 39 (06) : 2821 - 2827
  • [8] Breast cancer cell line MDA-MB 231 exerts a potent and direct anti-apoptotic effect on mature osteoclasts
    Gallet, M
    Sévenet, N
    Dupont, C
    Brazier, M
    Kamel, S
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2004, 319 (02) : 690 - 696
  • [9] A Novel All-trans Retinoid Acid Derivative Induces Apoptosis in MDA-MB-231 Breast Cancer Cells
    Wang, Bei
    Yan, Yun-Wen
    Zhou, Qing
    Gui, Shu-Yu
    Chen, Fei-Hu
    Wang, Yuan
    ASIAN PACIFIC JOURNAL OF CANCER PREVENTION, 2014, 15 (24) : 10819 - 10824
  • [10] Paxillin phosphorylation and complexing with Erk and FAK are regulated by PLD activity in MDA-MB-231 cells
    Pribic, Jelena
    Brazill, Derrick
    CELLULAR SIGNALLING, 2012, 24 (08) : 1531 - 1540