Hippo Pathway Overview

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The Hippo signaling pathway is a key regulator of organ size. The pathway was first identified in fruit flies, but was subsequently found to be an evolutionarily conserved pathway important in restraining cell proliferation and promoting apoptosis. The core signaling pathway is a protein kinase cascade composed of multiple proteins with identified orthologs in mammalian cells1.

The core proteins, MST1/2 (Hippo*), Salvadore-1, Lats1/2 (Warts) and Mob (Mats) comprise a protein kinase signaling cascade that phosphorylates YAP/TAZ (Yki). Phosphorylation results in binding of YAP/TAZ to 14-3-3 proteins and retention of the protein in the cytoplasm. In the absence of signaling, YAP/TAZ translocates into the nucleus, binds to DNA in concert with its binding partners, and initiates transcription of target genes that promote cell proliferation and inhibit apoptosis.

Defects in Hippo signaling, and subsequent lack of phosphorylation of YAP/TAZ, result in out of control growth and larger than normal (some might say, hippopotamus-sized) tissues. Not surprisingly, there is significant interest in the study of the Hippo pathway in human cancers. Cell culture and animal models, as well as studies of human cancers, have shown that dysregulation of Hippo signaling promotes carcinogenesis. This suggests that components of the Hippo pathway may be potential targets for novel drug development2. Continuing studies are focusing on understanding the integration of multiple signals involved in cell-cell contact, cell polarity and G protein coupled receptor signaling through the Hippo pathway3,4.

Detection of MST1,2/STK3,4 in FFPE human colon carcinoma by IHC.

Detection of MST1,2/STK3,4 in FFPE human colon carcinoma by IHC. Antibody: Rabbit anti- MST1,2/STK3,4 (IHC-00432). Secondary: HRP-conjugated goat anti-rabbit IgG (A120-501P). Substrate: DAB.

Detection of human PPP2R1A by WB of immunoprecipitates from HeLa lysate.

Detection of human PPP2R1A by WB of immunoprecipitates from HeLa lysate. Antibodies: Rabbit anti-PPP2R1A (A300-962A & A300-963A). Secondary: ReliaBLOT® reagents (WB120).



Below is the current listing of Bethyl antibodies involved in Hippo signaling pathway research:



1. Zhang J, Smolen GA, Haber DA. 2008. Negative regulation of YAP by LATS1 underscores evolutionary conservation of the Drosophila Hippo pathway. Cancer Res. Apr 15;68(8):2789-2794.

2. Huang JM, Nagatomo I, Suzuki E, Mizumo T, Kumagai T, Berezov A, Zhang H, Karlan B, Greene MI, Wang Q. 2013. YAP modified cancer cell sensitivity to EGFR and surviving inhibitors and is negatively regulated by the non-receptor type protein tyrosine phosphatase 14. Oncogene. Apr 23;32(17):2220–2229.

3. Guo C, Zhang X, Pfeifer GP. 2011. The tumor suppressor RASSF1A prevents dephosphorylation of the mammalian STE20-like kinases MST1 and MST2. J Biol Chem. Feb 25;286(8):6253–6261.

4. Huntoon CJ, Nye MD, Geng L, Peterson KL, Flatten KS, Haluska P, Kaufmann SH, Karnitz, LM. 2010. Heat shock protein 90 inhibition depletes LATS1 and LATS2, tow regulators of the mammalian Hippo tumor suppressor pathway. Cancer Res. Nov 1:70(21):8642–8650.