Phospho-YAP (Ser397) (D1E7Y) Rabbit mAb

YAP (Yes-associated protein, YAP65) was first identified based on its ability to associate with the SH3 domain of Yes. It also binds to other SH3 domain-containing proteins such as Nck, Crk, Src, and Abl (1). In addition to the SH3 binding motif, YAP contains a PDZ interaction motif, a coiled-coil domain, and WW domains (2-4). While initial studies of YAP all pointed towards a role in anchoring and targeting to specific subcellular compartments, subsequent studies showed that YAP is a transcriptional co-activator by virtue of its WW domain interacting with the PY motif (PPxY) of the transcription factor PEBP2 and other transcription factors (5). In its capacity as a transcriptional co-activator, YAP is now widely recognized as a central mediator of the Hippo Pathway, which plays a fundamental and widely conserved role in regulating tissue growth and organ size (6-8). Phosphorylation at multiple sites (e.g., Ser109, Ser127) by LATS kinases promotes YAP translocation from the nucleus to the cytoplasm, where it is sequestered through association with 14-3-3 proteins (7-9). These LATS-driven phosphorylation events serve to prime YAP for subsequent phosphorylation by CK1δ/ε in an adjacent phosphodegron, triggering proteasomal degradation of YAP (10).Phosphorylation of YAP at Ser397 (annotated as Ser381 by Zhao et al. 2010) primes YAP for subsequent phosphorylation by CK1δ/ε in an adjacent phosphodegron (9). Upon phosphorylation, the phosphodegron recruits the β-TrCP (SCF) ubiquitin ligase complex, which ubiquitinates YAP to trigger its proteolytic degradation in the proteasome. 1.Sudol, M. (1994) Oncogene 9, 2145-52. 2.Mohler, P.J. et al. (1999) J Cell Biol 147, 879-90. 3.Espanel, X. and Sudol, M. (2001) J Biol Chem 276, 14514-23. 4.Sudol, M. et al. (1995) FEBS Lett 369, 67-71. 5.Yagi, R. et al. (1999) EMBO J 18, 2551-62. 6.Dong, J. et al. (2007) Cell 130, 1120-33. 7.Zhao, B. et al. (2010) Genes Dev 24, 862-74. 8.Zhao, B. et al. (2007) Genes Dev 21, 2747-61. 9.Yu, F.X. et al. (2012) Cell 150, 780-91. 10.Zhao, B. et al. (2010) Genes Dev 24, 72-85. 11.Zhao, B. et al. (2010) Genes Dev 24, 72-85.