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

2014 ◽  
Vol 464 (1) ◽  
pp. 99-108 ◽  
Author(s):  
Magdalene Ameka ◽  
Michael P. Kahle ◽  
Mathew Perez-Neut ◽  
Saverio Gentile ◽  
Ahmed A. Mirza ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Tumour Cell ◽  
Breast Cancer Cells ◽  
Kinase Activity ◽  
Focal Adhesions ◽  
Scaffold Protein ◽  
Physical Association

MEKK2 associates with the scaffold protein paxillin in tumour cell focal adhesions, promoting paxillin ubiquitylation and redistribution to cytoplasm. MEKK2 silencing prolongs paxillin retention in focal adhesions. MEKK2 requires both kinase activity and physical association with paxillin to promote ubiquitylation.

scholarly journals Constitutive p21-activated Kinase (PAK) Activation in Breast Cancer Cells as a Result of Mislocalization of PAK to Focal Adhesions

2004 ◽  
Vol 15 (6) ◽  
pp. 2965-2977 ◽  
Author(s):  
Mary R. Stofega ◽  
Luraynne C. Sanders ◽  
Elisabeth M. Gardiner ◽  
Gary M. Bokoch
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Rho Gtpases ◽  
Breast Cancer Cells ◽  
Kinase Activity ◽  
Focal Adhesions ◽  
Breast Cancer Cell Lines ◽  
Cytoskeletal Remodeling ◽  
P21 Activated Kinase ◽  
Pak Kinase

Cytoskeletal remodeling is critical for cell adhesion, spreading, and motility. p21-activated kinase (PAK), an effector molecule of the Rho GTPases Rac and Cdc42, has been implicated in cytoskeletal remodeling and cell motility. PAK kinase activity and subcellular distribution are tightly regulated by rapid and transient localized Rac and Cdc42 activation, and by interactions mediated by adapter proteins. Here, we show that endogenous PAK is constitutively activated in certain breast cancer cell lines and that this active PAK is mislocalized to atypical focal adhesions in the absence of high levels of activated Rho GTPases. PAK localization to focal adhesions in these cells is independent of PAK kinase activity, NCK binding, or GTPase binding, but requires the association of PAK with PIX. Disruption of the PAK–PIX interaction with competitive peptides displaces PAK from focal adhesions and results in a substantial reduction in PAK hyperactivity. Moreover, disruption of the PAK–PIX interaction is associated with a dramatic decrease of PIX and paxillin in focal adhesions, indicating that PAK localization to these structures via PIX is required for the maintenance of paxillin- and PIX-containing focal adhesions. Abnormal regulation of PAK localization and activity may contribute to the tumorigenic properties of certain breast cancer cells.

Neddylation controls basal MKK7 kinase activity in breast cancer cells

Oncogene ◽  
2015 ◽  
Vol 35 (20) ◽  
pp. 2624-2633 ◽  
Author(s):  
T Zhu ◽  
J Wang ◽  
Y Pei ◽  
Q Wang ◽  
Y Wu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Kinase Activity

scholarly journals Nuclear ErbB2 represses DEPTOR transcription to inhibit autophagy in breast cancer cells

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Yanli Bi ◽  
Longyuan Gong ◽  
Pengyuan Liu ◽  
Xiufang Xiong ◽  
Yongchao Zhao
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Transcriptional Repression ◽  
Breast Cancer Cells ◽  
Kinase Activity ◽  
Nuclear Translocation ◽  
Extracellular Signals ◽  
Consensus Binding Sequence ◽  
Binding Sequence

AbstractErbB2, a classical receptor tyrosine kinase, is frequently overexpressed in breast cancer cells. Although the role of ErbB2 in the transmission of extracellular signals to intracellular matrix has been widely studied, the functions of nuclear ErbB2 remain largely elusive. Here, we report a novel function of nuclear ErbB2 in repressing the transcription of DEPTOR, a direct inhibitor of mTOR. Nuclear ErbB2 directly binds to the consensus binding sequence in the DEPTOR promoter to repress its transcription. The kinase activity of ErbB2 is required for its nuclear translocation and transcriptional repression of DEPTOR. Moreover, the repressed DEPTOR by nuclear ErbB2 inhibits the induction of autophagy by activating mTORC1. Thus, our study reveals a novel mechanism for autophagy regulation by functional ErbB2, which translocates to the nucleus and acts as a transcriptional regulator to suppress DEPTOR transcription, leading to activation of the PI3K/AKT/mTOR pathway to inhibit autophagy.

ARF1 regulates adhesion of MDA-MB-231 invasive breast cancer cells through formation of focal adhesions

2015 ◽  
Vol 27 (3) ◽  
pp. 403-415 ◽  
Author(s):  
Sabrina Schlienger ◽  
Rodrigo Alain Migueles Ramirez ◽  
Audrey Claing
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Invasive Breast Cancer ◽  
Breast Cancer Cells ◽  
Focal Adhesions
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