TGFBR1 binds to PARD6A, a component of tight junctions, and localizes to tight junctions irrespective of TGF-beta stimulation. The N-terminus of PARD6A, containing a PB1 domain necessary for interactions with PRKCZ, is necessary for binding to TGFBR1 (Ozdamar et al. 2005).PARD6A, bound to PARD3 and PRKCZ, is associated with tight junctions through JAM-A (Ebnet et al. 2001), which is bound to CGN (cingulin) (Bazzoni et al. 2000). CGN binds ARHGEF18 (p114RhoGEF), and ARHGEF18 recruits RHOA to tight junctions. Other components of the tight junction structure are not shown in this context (Terry et al. 2011). Junctional RHOA activity is required for maintenance of junctional integrity through regulation of actinomyosin cytoskeleton organization (Terry et al. 2011). This was inferred from experiments in which a recombinant mouse Pard6a and recombinant human TGFBR1 were studied in the context of endogenous mouse tight junctions.
Bazzoni, G, Martinez-Estrada, OM, Orsenigo, F, Cordenonsi, M, Citi, S, Dejana, E
Ozdamar, B, Bose, R, Barrios-Rodiles, M, Wang, HR, Zhang, Y, Wrana, JL
Terry, SJ, Zihni, C, Elbediwy, A, Vitiello, E, Leefa Chong San, IV, Balda, MS, Matter, K
Ebnet, K, Aurrand-Lions, M, Kuhn, A, Kiefer, F, Butz, S, Zander, K, Meyer zu Brickwedde, MK, Suzuki, A, Imhof, BA, Vestweber, D
Ebnet, K, Suzuki, A, Horikoshi, Y, Hirose, T, Meyer zu Brickwedde, MK, Ohno, S, Vestweber, D
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