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.
机构:
Univ Sao Paulo, Fac Pharmaceut Sci, Dept Pharm, 580 Prof Lineu Prestes Av, BR-05508500 Sao Paulo, BrazilUniv Sao Paulo, Fac Pharmaceut Sci, Dept Pharm, 580 Prof Lineu Prestes Av, BR-05508500 Sao Paulo, Brazil
Fernandes, Thais Batista
de Azevedo, Ricardo Alexandre
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Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo, BrazilUniv Sao Paulo, Fac Pharmaceut Sci, Dept Pharm, 580 Prof Lineu Prestes Av, BR-05508500 Sao Paulo, Brazil
de Azevedo, Ricardo Alexandre
Yang, Rosania
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Univ Sao Paulo, Fac Pharmaceut Sci, Dept Pharm, 580 Prof Lineu Prestes Av, BR-05508500 Sao Paulo, BrazilUniv Sao Paulo, Fac Pharmaceut Sci, Dept Pharm, 580 Prof Lineu Prestes Av, BR-05508500 Sao Paulo, Brazil
Yang, Rosania
Teixeira, Sarah Fernandes
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Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo, BrazilUniv Sao Paulo, Fac Pharmaceut Sci, Dept Pharm, 580 Prof Lineu Prestes Av, BR-05508500 Sao Paulo, Brazil
Teixeira, Sarah Fernandes
Goulart Trossini, Gustavo Henrique
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Univ Sao Paulo, Fac Pharmaceut Sci, Dept Pharm, 580 Prof Lineu Prestes Av, BR-05508500 Sao Paulo, BrazilUniv Sao Paulo, Fac Pharmaceut Sci, Dept Pharm, 580 Prof Lineu Prestes Av, BR-05508500 Sao Paulo, Brazil
Goulart Trossini, Gustavo Henrique
Marzagao Barbuto, Jose Alexandre
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Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo, BrazilUniv Sao Paulo, Fac Pharmaceut Sci, Dept Pharm, 580 Prof Lineu Prestes Av, BR-05508500 Sao Paulo, Brazil
Marzagao Barbuto, Jose Alexandre
Ferreira, Adilson Kleber
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Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo, BrazilUniv Sao Paulo, Fac Pharmaceut Sci, Dept Pharm, 580 Prof Lineu Prestes Av, BR-05508500 Sao Paulo, Brazil
Ferreira, Adilson Kleber
Parise-Filho, Roberto
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Univ Sao Paulo, Fac Pharmaceut Sci, Dept Pharm, 580 Prof Lineu Prestes Av, BR-05508500 Sao Paulo, BrazilUniv Sao Paulo, Fac Pharmaceut Sci, Dept Pharm, 580 Prof Lineu Prestes Av, BR-05508500 Sao Paulo, Brazil
机构:
Wayne State Univ, Dept Pathol, Sch Med, Karmanos Canc Inst, Detroit, MI 48201 USAWayne State Univ, Dept Pathol, Sch Med, Karmanos Canc Inst, Detroit, MI 48201 USA
Li, YW
Upadhyay, S
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Wayne State Univ, Dept Pathol, Sch Med, Karmanos Canc Inst, Detroit, MI 48201 USAWayne State Univ, Dept Pathol, Sch Med, Karmanos Canc Inst, Detroit, MI 48201 USA
Upadhyay, S
Bhuiyan, M
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Wayne State Univ, Dept Pathol, Sch Med, Karmanos Canc Inst, Detroit, MI 48201 USAWayne State Univ, Dept Pathol, Sch Med, Karmanos Canc Inst, Detroit, MI 48201 USA
Bhuiyan, M
Sarkar, FH
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Wayne State Univ, Dept Pathol, Sch Med, Karmanos Canc Inst, Detroit, MI 48201 USAWayne State Univ, Dept Pathol, Sch Med, Karmanos Canc Inst, Detroit, MI 48201 USA
机构:
Fac Med Monastir, Unite Mecanismes Mol & Pathol 05 UR 09 09, Monastir 5019, Tunisia
Grenoble Inst Neurosci Calcium Channels Funct & P, INSERM, U836, F-38042 Grenoble 9, France
Univ Grenoble 1, F-38042 Grenoble 9, FranceFac Med Monastir, Unite Mecanismes Mol & Pathol 05 UR 09 09, Monastir 5019, Tunisia
Aroui, Sonia
Brahim, Souhir
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Fac Med Monastir, Unite Mecanismes Mol & Pathol 05 UR 09 09, Monastir 5019, TunisiaFac Med Monastir, Unite Mecanismes Mol & Pathol 05 UR 09 09, Monastir 5019, Tunisia
Brahim, Souhir
Hamelin, Jocelyne
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Fac Pharm Chatenay Malabry, INSERM, U749, F-92290 Chatenay Malabry, FranceFac Med Monastir, Unite Mecanismes Mol & Pathol 05 UR 09 09, Monastir 5019, Tunisia
Hamelin, Jocelyne
De Waard, Michel
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Grenoble Inst Neurosci Calcium Channels Funct & P, INSERM, U836, F-38042 Grenoble 9, France
Univ Grenoble 1, F-38042 Grenoble 9, FranceFac Med Monastir, Unite Mecanismes Mol & Pathol 05 UR 09 09, Monastir 5019, Tunisia
De Waard, Michel
Breard, Jacqueline
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Fac Pharm Chatenay Malabry, INSERM, U749, F-92290 Chatenay Malabry, FranceFac Med Monastir, Unite Mecanismes Mol & Pathol 05 UR 09 09, Monastir 5019, Tunisia
Breard, Jacqueline
Kenani, Abderraouf
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Fac Med Monastir, Unite Mecanismes Mol & Pathol 05 UR 09 09, Monastir 5019, TunisiaFac Med Monastir, Unite Mecanismes Mol & Pathol 05 UR 09 09, Monastir 5019, Tunisia