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Gene correction of integrin β4-dependent pyloric atresia-junctional epidermolysis bullosa keratinocytes estableshes a role for β4 tyrosines 1422 and 1440 in hemidesmosome assembly
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Dellambra E., Prislei S., Salvati A.L., Madeddu M.L., Golisano O., Siveiro E., Bondanza S., Cicuzza S., Orecchia A., Giancotti F.G., et al. Gene correction of integrin β4-dependent pyloric atresia-junctional epidermolysis bullosa keratinocytes estableshes a role for β4 tyrosines 1422 and 1440 in hemidesmosome assembly. J Biol Chem 276 (2001) 41336-41342
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(2001)
J Biol Chem
, vol.276
, pp. 41336-41342
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Dellambra, E.1
Prislei, S.2
Salvati, A.L.3
Madeddu, M.L.4
Golisano, O.5
Siveiro, E.6
Bondanza, S.7
Cicuzza, S.8
Orecchia, A.9
Giancotti, F.G.10
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44
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0041326890
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α6β4 integrin regulates keratinocyte chemotaxis through differential GTPase activation and antagonism of α3β1 integrin
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Russell A.J., Fincher E.F., Millman L., Smith R., Vela V., Waterman E.A., Dey C.N., Guide S., Weaver V.M., and Marinkovich M.P. α6β4 integrin regulates keratinocyte chemotaxis through differential GTPase activation and antagonism of α3β1 integrin. J Cell Sci 116 (2003) 3543-3556
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(2003)
J Cell Sci
, vol.116
, pp. 3543-3556
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Russell, A.J.1
Fincher, E.F.2
Millman, L.3
Smith, R.4
Vela, V.5
Waterman, E.A.6
Dey, C.N.7
Guide, S.8
Weaver, V.M.9
Marinkovich, M.P.10
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45
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0032845770
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Protein kinase C-dependent mobilization of the α6β4 integrin from hemidesmosomes and its association with actin-rich cell protrusions drive the chemotactic migration of carcinoma cells
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Rabinovitz I., Toker A., and Mercurio A.M. Protein kinase C-dependent mobilization of the α6β4 integrin from hemidesmosomes and its association with actin-rich cell protrusions drive the chemotactic migration of carcinoma cells. J Cell Biol 146 (1999) 1147-1159
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(1999)
J Cell Biol
, vol.146
, pp. 1147-1159
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Rabinovitz, I.1
Toker, A.2
Mercurio, A.M.3
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46
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0035354189
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Protein kinase Cδ-mediated phosphorylation of α6β4 is associated with reduced integrin localization to the hemidesmosome and decreased keratinocyte attachment
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459104598. This study demonstrates that the activation of PKCδ in primary mouse keratinocytes leads to a redistribution of α6β4 from HDs to the cytosol and a reduced cell attachment to laminin, indicating that serine phosphorylations mediate HD disassembly.
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Alt A., Ohba M., Li L., Gartsbein M., Belanger A., Denning M.F., Kuroki T., Yuspa S.H., and Tennenbaum T. Protein kinase Cδ-mediated phosphorylation of α6β4 is associated with reduced integrin localization to the hemidesmosome and decreased keratinocyte attachment. Cancer Res 61 (2001) 459104598. This study demonstrates that the activation of PKCδ in primary mouse keratinocytes leads to a redistribution of α6β4 from HDs to the cytosol and a reduced cell attachment to laminin, indicating that serine phosphorylations mediate HD disassembly.
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(2001)
Cancer Res
, vol.61
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Alt, A.1
Ohba, M.2
Li, L.3
Gartsbein, M.4
Belanger, A.5
Denning, M.F.6
Kuroki, T.7
Yuspa, S.H.8
Tennenbaum, T.9
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47
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2942628076
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Protein kinase C-α phosphorylation of specific serines in the connecting segment of the β4 integrin regulates the dynamics of type II hemidesmosomes
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The first of two papers using phosphopeptide mapping to identify serines 1356, 1360, and 1364 in the β4 CS as critical residues for HD disassembly. The phosphorylation of these sites was induced by EGF and at least two of the three serines were phosphorylated by PKCα in HaCaT cells. These phosphorylations were associated with HD destabilization using mutants carrying aspartic acid or alanine substitutions overexpressed in COS-7.
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Rabinovitz I., Tsomo L., and Mercurio A.M. Protein kinase C-α phosphorylation of specific serines in the connecting segment of the β4 integrin regulates the dynamics of type II hemidesmosomes. Mol Cell Biol 24 (2004) 4351-4360. The first of two papers using phosphopeptide mapping to identify serines 1356, 1360, and 1364 in the β4 CS as critical residues for HD disassembly. The phosphorylation of these sites was induced by EGF and at least two of the three serines were phosphorylated by PKCα in HaCaT cells. These phosphorylations were associated with HD destabilization using mutants carrying aspartic acid or alanine substitutions overexpressed in COS-7.
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(2004)
Mol Cell Biol
, vol.24
, pp. 4351-4360
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Rabinovitz, I.1
Tsomo, L.2
Mercurio, A.M.3
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48
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34548477663
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Serine phosphorylation of the integrin β4 subunit is necessary for epidermal growth factor-induced hemidesmosome disruption
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This is an elegant work demonstrating serines 1356, 1360, 1364 as important phosphorylation sites involved in EGF-induced HD disassembly in human keratinocytes. S1360 and S1364 were identified as sites for PKC and PKA, respectively. Using mutants carrying aspartic acid or alanine substitutions, it was shown that the phosphorylation of two or more of the serines prevents binding of the plectin ABD to β4. Whereas triple aspartic acid mutations prevented HD assembly, substitution to the same residues to alanines provided partial protection against EGF-induced HD disassembly.
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Wilhelmsen K., Litjens S.H.M., Kuikman I., Margadant C., van Rheenen J., and Sonnenberg A. Serine phosphorylation of the integrin β4 subunit is necessary for epidermal growth factor-induced hemidesmosome disruption. Mol Biol Cell 18 (2007) 3512-3522. This is an elegant work demonstrating serines 1356, 1360, 1364 as important phosphorylation sites involved in EGF-induced HD disassembly in human keratinocytes. S1360 and S1364 were identified as sites for PKC and PKA, respectively. Using mutants carrying aspartic acid or alanine substitutions, it was shown that the phosphorylation of two or more of the serines prevents binding of the plectin ABD to β4. Whereas triple aspartic acid mutations prevented HD assembly, substitution to the same residues to alanines provided partial protection against EGF-induced HD disassembly.
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(2007)
Mol Biol Cell
, vol.18
, pp. 3512-3522
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Wilhelmsen, K.1
Litjens, S.H.M.2
Kuikman, I.3
Margadant, C.4
van Rheenen, J.5
Sonnenberg, A.6
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49
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27644496163
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Mobilization and activation of a signaling competent α6β4 integrin underlies its contribution to carcinoma progression
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Lipscomb E.A., and Mercurio A.M. Mobilization and activation of a signaling competent α6β4 integrin underlies its contribution to carcinoma progression. Cancer Metastasis Rev 24 (2005) 413-423
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(2005)
Cancer Metastasis Rev
, vol.24
, pp. 413-423
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Lipscomb, E.A.1
Mercurio, A.M.2
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50
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21744455891
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Targeted deletion of the integrin β4 cytoplasmic domain suppresses laminin-5 dependent nuclear entry of mitogen activated protein kinases and NF-κB, causing defects in epidermal growth and migration
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In this study, mice were generated carrying a targeted deletion of the cytoplasmic domain of β4 downstream of residue 1355. Despite epidermal hypoplasia and reduced wound healing, HD formation and stable adhesion to the BM in these mice were not impaired, demonstrating that the part upstream of residue 1355 that interacts with plectin is sufficient for HD assembly, whereas the downstream segment containing the serines and tyrosine described in the literature is not essential.
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Nikolopoulos S.N., Blaikie P., Yoshioka T., Guo W., Puri C., Tacchetti C., and Giancotti F.G. Targeted deletion of the integrin β4 cytoplasmic domain suppresses laminin-5 dependent nuclear entry of mitogen activated protein kinases and NF-κB, causing defects in epidermal growth and migration. Mol Cell Biol 25 (2005) 6090-6102. In this study, mice were generated carrying a targeted deletion of the cytoplasmic domain of β4 downstream of residue 1355. Despite epidermal hypoplasia and reduced wound healing, HD formation and stable adhesion to the BM in these mice were not impaired, demonstrating that the part upstream of residue 1355 that interacts with plectin is sufficient for HD assembly, whereas the downstream segment containing the serines and tyrosine described in the literature is not essential.
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(2005)
Mol Cell Biol
, vol.25
, pp. 6090-6102
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Nikolopoulos, S.N.1
Blaikie, P.2
Yoshioka, T.3
Guo, W.4
Puri, C.5
Tacchetti, C.6
Giancotti, F.G.7
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51
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0032857374
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Transmembrane signaling for adhesive regulation of desmosomes and hemidesmosomes, and for cell-cell detachment induced by pemphigus IgG in cultures keratinocytes: involvement of protein kinase C
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Kitajima Y., Aoyama Y., and Seishima M. Transmembrane signaling for adhesive regulation of desmosomes and hemidesmosomes, and for cell-cell detachment induced by pemphigus IgG in cultures keratinocytes: involvement of protein kinase C. J Investig Dermatol Symp Proc 4 (1999) 137-144
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(1999)
J Investig Dermatol Symp Proc
, vol.4
, pp. 137-144
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Kitajima, Y.1
Aoyama, Y.2
Seishima, M.3
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52
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0042679580
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The MSP receptor regulates alpha6beta4 and alpha3beta1 integrins via 14-3-3 proteins in keratinocyte migration
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A very interesting report demonstrating that stimulation of human keratinocytes with the Ron ligand MSP induces serine phosphorylation of both β4 and Ron at specific 14-3-3-binding sites, resulting in the 14-3-3-dependent formation of a Ron-α6β4 complex that result in the translocation of α6β4 from HDs to lamellipodia. This report thus emphasizes the importance of serine phosphorylations on integrin α6β4 in response to a physiological stimulus that induces HD disassembly and wound healing. In addition, it provides potential mechanism for serine phosphorylation-mediated HD disruption.
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Santoro M.M., Gaudino G., and Marchisio P.C. The MSP receptor regulates alpha6beta4 and alpha3beta1 integrins via 14-3-3 proteins in keratinocyte migration. Dev Cell 5 (2003) 257-271. A very interesting report demonstrating that stimulation of human keratinocytes with the Ron ligand MSP induces serine phosphorylation of both β4 and Ron at specific 14-3-3-binding sites, resulting in the 14-3-3-dependent formation of a Ron-α6β4 complex that result in the translocation of α6β4 from HDs to lamellipodia. This report thus emphasizes the importance of serine phosphorylations on integrin α6β4 in response to a physiological stimulus that induces HD disassembly and wound healing. In addition, it provides potential mechanism for serine phosphorylation-mediated HD disruption.
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(2003)
Dev Cell
, vol.5
, pp. 257-271
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Santoro, M.M.1
Gaudino, G.2
Marchisio, P.C.3
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