77. Hilbig D, Sittig D, Hoffmann F,
Rothemund S, Warmt E, Quaas M,
Stu ¨rmer J, Seiler L, Liebscher I, Hoang NA,
K€ as JA, Banks L, Aust G (2018) Mechanodependent
phosphorylation
of
the
PDZ-binding Motif of CD97/ADGRE5
modulates cellular detachment. Cell Rep
24:1986–1995
78. Sivaramakrishnan S, Schneider JL, Sitikov A,
Goldman RD, Ridge KM (2009) Shear stress
induced reorganization of the keratin intermediate filament network requires phosphorylation by protein kinase C ζ. Mol Biol Cell
20:2755–2765
79. O’Neill AK, Gallegos LL, Justilien V, Garcia
EL, Leitges M, Fields A, Hall RA, Newton AC
(2011) PKCα interacts with its novel substrate
discs large homolog (DLG) 1 to promote
cellular migration. J Biol Chem jbc.
M111.294603
80. Kanzaki N, Ogita H, Komura H, Ozaki M,
Sakamoto Y, Majima T, Ijuin T, Takenawa T,
Takai Y (2008) Involvement of the nectinafadin complex in PDGF-induced cell survival. J Cell Sci 121:2008–2017
81. Sato T, Fujita N, Yamada A, Ooshio T,
Okamoto R, Irie K, Takai Y (2006) Regulation of the assembly and adhesion activity of
E-cadherin by nectin and afadin for the formation of adherens junctions in Madin-Darby
canine kidney cells. J Biol Chem
281:5288–5299
82. Ooshio T, Kobayashi R, Ikeda W, Miyata M,
Fukumoto Y, Matsuzawa N, Ogita H, Takai Y
(2010) Involvement of the interaction of afadin with ZO-1 in the formation of tight junctions in Madin-Darby canine kidney cells. J
Biol Chem 285:5003–5012
83. Severson EA, Lee WY, Capaldo CT, Nusrat A,
Parkos CA (2009) Junctional adhesion molecule A interacts with afadin and PDZ-GEF2
to activate Rap1A, regulate β1 integrin levels,
and enhance cell migration. Mol Biol Cell
20:1916–1925
84. Asada M, Irie K, Morimoto K, Yamada A,
Ikeda W, Takeuchi M, Takai Y (2003) ADIP,
a novel afadin- and α-actinin-binding protein
localized at cell-cell adherens junctions. J Biol
Chem 278:4103–4111
85. Mandai K, Nakanishi H, Satoh A, Obaishi H,
Wada M, Nishioka H, Itoh M, Mizoguchi A,
Aoki T, Fujimoto T, Matsuda Y, Tsukita S,
Takai Y (1997) Afadin: a novel actin
filament-binding protein with one PDZ
domain localized at cadherin-based cell-tocell adherens junction. J Cell Biol
139:517–528
86. Mandai K, Nakanishi H, Satoh A,
Takahashi K, Satoh K, Nishioka H,
Mizoguchi A, Takai Y (1999) Ponsin/
SH3P12: an l-afadin– and vinculin-binding
protein localized at cell–cell and cell–matrix
adherens
junctions.
J
Cell
Biol
144:1001–1018
87. Ooshio T, Irie K, Morimoto K, Fukuhara A,
Imai T, Takai Y (2004) Involvement of
LMO7 in the association of two cell-cell adhesion molecules, nectin and E-cadherin,
through afadin and alpha-actinin in epithelial
cells. J Biol Chem 279:31365–31373
88. Takai Y, Nakanishi H (2003) Nectin and afadin: novel organizers of intercellular junctions. J Cell Sci 116:17–27
89. Monteiro AC, Sumagin R, Rankin CR,
Leoni G, Mina MJ, Reiter DM, Stehle T,
Dermody TS, Schaefer SA, Hall RA,
Nusrat A, Parkos CA (2013) JAM-A associates with ZO-2, afadin, and PDZ-GEF1 to
activate Rap2c and regulate epithelial barrier
function. Mol Biol Cell 24:2849–2860
90. Fanning AS, Van Itallie CM, Anderson JM
(2012) Zonula occludens-1 and -2 regulate
apical cell structure and the zonula adherens
cytoskeleton in polarized epithelia. Mol Biol
Cell 23:577–590
91. Miyata M, Rikitake Y, Takahashi M,
Nagamatsu Y, Yamauchi Y, Ogita H,
Hirata K, Takai Y (2009) Regulation by afadin
of cyclical activation and inactivation of Rap1,
Rac1, and RhoA small G proteins at leading
edges of moving NIH3T3 cells. J Biol Chem
284:24595–24609
92. Choi W, Acharya BR, Peyret G, Fardin M-A,
Me `ge R-M, Ladoux B, Yap AS, Fanning AS,
Peifer M (2016) Remodeling the zonula
adherens in response to tension and the role
of afadin in this response. J Cell Biol
213:243–260
93. Ebnet K, Schulz CU, Zu Brickwedde M-KM,
Pendl GG, Vestweber D (2000) Junctional
adhesion molecule interacts with the PDZ
domain-containing proteins AF-6 and ZO-1.
J Biol Chem 275:27979–27988
94. Scott DW, Tolbert CE, Burridge K (2016)
Tension on JAM-A activates RhoA via
GEF-H1 and p115 RhoGEF. Mol Biol Cell
27:1420–1430
95. Priya R, Yap AS (2015) Active tension: the
role of cadherin adhesion and signaling in
generating junctional contractility. Curr Top
Dev Biol 112:65–102
96. Iden S, Misselwitz S, Peddibhotla SSD,
Tuncay H, Rehder D, Gerke V, Robenek H,
Suzuki A, Ebnet K (2012) aPKC
Mechanoregulation of PDZ Proteins
273
Rothemund S, Warmt E, Quaas M,
Stu ¨rmer J, Seiler L, Liebscher I, Hoang NA,
K€ as JA, Banks L, Aust G (2018) Mechanodependent
phosphorylation
of
the
PDZ-binding Motif of CD97/ADGRE5
modulates cellular detachment. Cell Rep
24:1986–1995
78. Sivaramakrishnan S, Schneider JL, Sitikov A,
Goldman RD, Ridge KM (2009) Shear stress
induced reorganization of the keratin intermediate filament network requires phosphorylation by protein kinase C ζ. Mol Biol Cell
20:2755–2765
79. O’Neill AK, Gallegos LL, Justilien V, Garcia
EL, Leitges M, Fields A, Hall RA, Newton AC
(2011) PKCα interacts with its novel substrate
discs large homolog (DLG) 1 to promote
cellular migration. J Biol Chem jbc.
M111.294603
80. Kanzaki N, Ogita H, Komura H, Ozaki M,
Sakamoto Y, Majima T, Ijuin T, Takenawa T,
Takai Y (2008) Involvement of the nectinafadin complex in PDGF-induced cell survival. J Cell Sci 121:2008–2017
81. Sato T, Fujita N, Yamada A, Ooshio T,
Okamoto R, Irie K, Takai Y (2006) Regulation of the assembly and adhesion activity of
E-cadherin by nectin and afadin for the formation of adherens junctions in Madin-Darby
canine kidney cells. J Biol Chem
281:5288–5299
82. Ooshio T, Kobayashi R, Ikeda W, Miyata M,
Fukumoto Y, Matsuzawa N, Ogita H, Takai Y
(2010) Involvement of the interaction of afadin with ZO-1 in the formation of tight junctions in Madin-Darby canine kidney cells. J
Biol Chem 285:5003–5012
83. Severson EA, Lee WY, Capaldo CT, Nusrat A,
Parkos CA (2009) Junctional adhesion molecule A interacts with afadin and PDZ-GEF2
to activate Rap1A, regulate β1 integrin levels,
and enhance cell migration. Mol Biol Cell
20:1916–1925
84. Asada M, Irie K, Morimoto K, Yamada A,
Ikeda W, Takeuchi M, Takai Y (2003) ADIP,
a novel afadin- and α-actinin-binding protein
localized at cell-cell adherens junctions. J Biol
Chem 278:4103–4111
85. Mandai K, Nakanishi H, Satoh A, Obaishi H,
Wada M, Nishioka H, Itoh M, Mizoguchi A,
Aoki T, Fujimoto T, Matsuda Y, Tsukita S,
Takai Y (1997) Afadin: a novel actin
filament-binding protein with one PDZ
domain localized at cadherin-based cell-tocell adherens junction. J Cell Biol
139:517–528
86. Mandai K, Nakanishi H, Satoh A,
Takahashi K, Satoh K, Nishioka H,
Mizoguchi A, Takai Y (1999) Ponsin/
SH3P12: an l-afadin– and vinculin-binding
protein localized at cell–cell and cell–matrix
adherens
junctions.
J
Cell
Biol
144:1001–1018
87. Ooshio T, Irie K, Morimoto K, Fukuhara A,
Imai T, Takai Y (2004) Involvement of
LMO7 in the association of two cell-cell adhesion molecules, nectin and E-cadherin,
through afadin and alpha-actinin in epithelial
cells. J Biol Chem 279:31365–31373
88. Takai Y, Nakanishi H (2003) Nectin and afadin: novel organizers of intercellular junctions. J Cell Sci 116:17–27
89. Monteiro AC, Sumagin R, Rankin CR,
Leoni G, Mina MJ, Reiter DM, Stehle T,
Dermody TS, Schaefer SA, Hall RA,
Nusrat A, Parkos CA (2013) JAM-A associates with ZO-2, afadin, and PDZ-GEF1 to
activate Rap2c and regulate epithelial barrier
function. Mol Biol Cell 24:2849–2860
90. Fanning AS, Van Itallie CM, Anderson JM
(2012) Zonula occludens-1 and -2 regulate
apical cell structure and the zonula adherens
cytoskeleton in polarized epithelia. Mol Biol
Cell 23:577–590
91. Miyata M, Rikitake Y, Takahashi M,
Nagamatsu Y, Yamauchi Y, Ogita H,
Hirata K, Takai Y (2009) Regulation by afadin
of cyclical activation and inactivation of Rap1,
Rac1, and RhoA small G proteins at leading
edges of moving NIH3T3 cells. J Biol Chem
284:24595–24609
92. Choi W, Acharya BR, Peyret G, Fardin M-A,
Me `ge R-M, Ladoux B, Yap AS, Fanning AS,
Peifer M (2016) Remodeling the zonula
adherens in response to tension and the role
of afadin in this response. J Cell Biol
213:243–260
93. Ebnet K, Schulz CU, Zu Brickwedde M-KM,
Pendl GG, Vestweber D (2000) Junctional
adhesion molecule interacts with the PDZ
domain-containing proteins AF-6 and ZO-1.
J Biol Chem 275:27979–27988
94. Scott DW, Tolbert CE, Burridge K (2016)
Tension on JAM-A activates RhoA via
GEF-H1 and p115 RhoGEF. Mol Biol Cell
27:1420–1430
95. Priya R, Yap AS (2015) Active tension: the
role of cadherin adhesion and signaling in
generating junctional contractility. Curr Top
Dev Biol 112:65–102
96. Iden S, Misselwitz S, Peddibhotla SSD,
Tuncay H, Rehder D, Gerke V, Robenek H,
Suzuki A, Ebnet K (2012) aPKC
Mechanoregulation of PDZ Proteins
273