title: The regulatory or phosphorylation domain of p120 catenin controls E-cadherin dynamics at the plasma membrane.
abstract: In contrast to growth factor-stimulated tyrosine phosphorylation of p120, its relatively constitutive serine/threonine phosphorylation is not well understood. Here we examined the role of serine/threonine phosphorylation of p120 in cadherin function. Expression of cadherins in cadherin-null cells converted them to an epithelial phenotype, induced p120 phosphorylation and localized it to sites of cell contact. Detergent solubility and immunofluorescence confirmed that phosphorylated p120 was at the plasma membrane. E-cadherin constructs incapable of traveling to the plasma membrane did not induce serine/threonine phosphorylation of p120, nor did cadherins constructs incapable of binding p120. However, an E-cadherin cytoplasmic domain construct artificially targeted to the plasma membrane did induce serine/threonine phosphorylation of p120, suggesting phosphorylation occurs independently of signals from cadherin dimerization and trafficking through the ER/Golgi. Solubility assays following calcium switch showed that p120 isoform 3A was more effective at stabilizing E-cadherin at the plasma membrane relative to isoform 4A. Since the major phosphorylation domain of p120 is included in isoform 3A but not 4A, we tested p120 mutated in the known phosphorylation sites in this domain and found that it was even less effective at stabilizing E-cadherin. These data suggest that serine/threonine phosphorylation of p120 influences the dynamics of E-cadherin in junctions.
authors: Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198-7696, USA.
authors: Yuri
authors: Y
authors: Fukumoto
authors: Yasushi
authors: Y
authors: Shintani
authors: Albert B
authors: AB
authors: Reynolds
authors: Keith R
authors: KR
authors: Johnson
authors: Margaret J
authors: MJ
authors: Wheelock
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000502:physiology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D051177:Catenins; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D004705:Endocytosis / Q000502:physiology; D006801:Humans; D007365:Intercellular Junctions / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051379:Mice; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding / Q000502:physiology; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D012694:Serine / Q000378:metabolism; D012995:Solubility; D013912:Threonine / Q000378:metabolism; D000095002:Delta Catenin
chemical_list: D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D010750:Phosphoproteins; D020033:Protein Isoforms; D013912:Threonine; D012694:Serine; D000095002:Delta Catenin
references: J Cell Biol. 2000 Dec 11;151(6):1193-206
references: 11121435
references: Mol Cell Biol. 2007 Mar;27(5):1745-57
references: 17194753
references: J Cell Biol. 2002 Nov 11;159(3):465-76
references: 12427869
references: Differentiation. 2002 Dec;70(9-10):583-9
references: 12492499
references: J Biol Chem. 2003 May 9;278(19):17269-76
references: 12604612
references: Biochemistry. 2003 Aug 5;42(30):9195-204
references: 12885254
references: Annu Rev Cell Dev Biol. 2003;19:207-35
references: 14570569
references: J Cell Biol. 2003 Nov 10;163(3):525-34
references: 14610055
references: Oncogene. 2004 Oct 18;23(48):7947-56
references: 15489912
references: Cancer Res. 1989 Apr 15;49(8):2128-33
references: 2702654
references: J Cell Biol. 1989 Oct;109(4 Pt 1):1787-94
references: 2793940
references: J Cell Biol. 1990 Oct;111(4):1645-50
references: 2211831
references: Mol Cell Biol. 1991 Feb;11(2):713-20
references: 1703631
references: J Cell Biol. 1991 Apr;113(1):173-85
references: 2007622
references: J Cell Biol. 1991 Jul;114(2):319-27
references: 1649199
references: J Cell Sci. 1992 May;102 ( Pt 1):7-17
references: 1500442
references: Oncogene. 1992 Dec;7(12):2439-45
references: 1334250
references: J Cell Sci. 2004 Mar 15;117(Pt 8):1339-50
references: 14996911
references: Oncogene. 2004 Jul 15;23(32):5532-42
references: 15107817
references: J Biol Chem. 2004 Jul 23;279(30):31041-9
references: 15143071
references: J Cell Biol. 1999 Dec 13;147(6):1325-40
references: 10601344
references: J Cell Biol. 2000 Jan 10;148(1):189-202
references: 10629228
references: J Cell Sci. 2000 Apr;113 ( Pt 8):1319-34
references: 10725216
references: Nat Cell Biol. 2000 Sep;2(9):637-44
references: 10980705
references: Exp Cell Res. 1993 Aug;207(2):252-60
references: 8344378
references: J Cell Sci. 1993 Sep;106 ( Pt 1):401-9
references: 8270638
references: J Biol Chem. 1994 Apr 22;269(16):12092-8
references: 8163513
references: Mol Cell Biol. 1994 Dec;14(12):8333-42
references: 7526156
references: Curr Opin Cell Biol. 1995 Oct;7(5):619-27
references: 8573335
references: Biotechniques. 1997 Jul;23(1):96-7
references: 9232237
references: J Biol Chem. 1997 Dec 12;272(50):31894-901
references: 9395537
references: FEBS Lett. 1998 Nov 6;438(3):306-10
references: 9827567
references: Biochem J. 1999 Mar 1;338 ( Pt 2):471-8
references: 10024525
references: J Cell Sci. 1999 Apr;112 ( Pt 8):1149-58
references: 10085250
references: J Cell Sci. 1999 May;112 ( Pt 10):1621-32
references: 10212155
references: J Cell Biol. 1999 May 3;145(3):551-62
references: 10225956
references: J Cell Biol. 1999 Jul 12;146(1):219-32
references: 10402472
references: J Biol Chem. 1999 Jul 23;274(30):21409-15
references: 10409703
references: Hybrid Hybridomics. 2004 Dec;23(6):343-51
references: 15684660
references: J Cell Sci. 2005 Mar 1;118(Pt 5):873-87
references: 15713751
references: Exp Cell Res. 2006 Oct 15;312(17):3336-48
references: 16935280
references: Cell. 2006 Dec 1;127(5):1027-39
references: 17129786
references: Biochim Biophys Acta. 2007 Jan;1773(1):47-58
references: 16904204
references: J Cell Sci. 2001 Feb;114(Pt 3):503-12
references: 11171320