The SARAH (Sav/Rassf/Hpo) domain is found at the C terminus in three classes of eukaryotic tumour suppressors that give the domain its name. In the Sav (Salvador) and Hpo (Hippo) families, the SARAH domain mediates signal transduction from Hpo via the Sav scaffolding protein to the downstream component Wts (Warts); the phosphorylation of Wts by Hpo triggers cell cycle arrest and apoptosis by down-regulating cyclin E, Diap 1 and other targets [, ]. The SARAH domain is also involved in dimerisation, as in the human Hpo orthologue, Mst1, which homodimerises via its C-terminal SARAH domain. The SARAH domain is found associated with other domains, such as protein kinase domains, WW/rsp5/WWP domain (), C1 domain (), LIM domain (), or the Ras-associating (RA) domain ().This entry represents the C-terminal SARAH domain of Mst1. The Mst1 SARAH domain interacts with Rassf1 and Rassf5 by forming a heterodimer which mediates the apoptosis process [].
This entry includes hepatocyte growth factor (HGF; also called scatter factor) and HGF-like proteins (also known as macrophage stimulatory protein, MST1). Hepatocyte growth factor (HGF) is an activating ligand of the Met receptor tyrosine kinase, whose activity is essential for normal tissue development and organ regeneration []. HGF is essential for placental, liver, and muscle development, whereas MST1 is not required for embryogenesis, fertility, or wound healing. Genes for HGF and its receptor, the Met tyrosine kinase, are close together on chromosome 7, so that polysomy of chromosome 7 may contribute to malignancy through overproduction of both molecules. MST1 and its receptor, the Ron tyrosine kinase, are close together on chromosome 3. HGF and MST1 are closely related to plasminogen, having similar domain architecture: signal sequence followed by a PAN (formerly apple) domain, four (rather than five) kringle domains, and a trypsin domain, which appears to lack any peptidase activity.
