The Essence of the Hippo Signalling System - Therapeutic Strategies in Cancer Biology and Pathology - page 135

Table 25.1 The Hippo Signalling Components, Their Possible Upstream Regulators and the
Interacting Signalling Systems That Determine Phenotypic Outcomes

Upstream Regulators and
Activators

Activator Identity Function

Fat Fat4
Dachsous Dchs1, Dchs2

Atypical cadherins Cell adhesion, motility,

proliferation, apoptosis

Four jointed Fat signalling Ser/Thr kinase

Merlin/NF2
Kibra

CD44 Transmembrane receptor

implicated in cell adhesion,
metastasis
FERM-domain adaptor protein
WW-domain adaptor protein

RASSF1-6 RA-domain adaptor

Signalling Component Kinase Identification Function/Target

Hippo MST1, MST2 Ste20 family Ser/Thr kinase

Sav1 (WW45) WW-domain adaptor

Lats1, Lats2 NDR Ser/Thr kinases

Mats Co-factor of Lats1 and Lats2

YAP/Yorkie/Taz WW-domain transcription

co-factors

Interacting Signalling
Systems

Phenotypic Outcome

P53
Growth factors

Cell cycle regulation, apoptosis
Cell proliferation, EMT

TGF-β YAP-mediated

sequestration of Smads

Inhibition of TGF-β
Signalling

AREG YAP induces AREG

expression

EGFR-mediated induction of
cell proliferation and invasion

Connective tissue growth
factor

YAP-dependent induction AREG and HB-EGF via

activation of EGFR

Hh YA P Inhibition of neuronal

differentiation

Wnt/β-catenin
Ras/ERK

YAP and TAZ bind to
β-catenin

Interference with nuclear
translocation, Wnt signalling
inhibited

Source : This is based on information derived from Halder and Johnson (2011), Sherbet (2011a) and references cited in
the text.

Signalling components of the Hippo system are characterised by the presence of
the SARAH (Salvador 1/RASSF1A/Hippo) and WW domains that mediate inter-
action with other proteins. The SARAH domain mediates the interaction between
RASSF1 and MST1 and MST2. SARAH possibly also mediates coupling of