Biomedical Engineering Reference
In-Depth Information
Celsr1
Wnt5
Fat
Gpc4
Lrp5/6
Cthrc1
Ror2
Wnt
Wnt
Wnt11
Fzd
Vangl2
Fzd7
Fzd
Dsh
Pk
Dsh
Dsh
Axin
GSK3
b
-cat
APC
RhoA
Ca
2+
PKC
Rac
Four-jointed
Rock
CamKII
JNK
b
-cat
TCF/Lef
ATF2
NFAT
Target gene expression
Actin cytoskeleton
Figure 4.3 Divergence of the Wnt pathways in vertebrates. The Wnt/b-catenin pathway (
pathway) involves stabilization of
b-catenin upon binding of Wnt ligand to Fzd and Lrp5/6 receptors, leading to target gene expression mediated by b-catenin and TCF/
Lef. The Wnt/planar cell polarity (PCP) pathway (a
“
canonical
”
pathway) primarily regulates actin cytoskeleton via several groups of mol-
ecules, including PCP core molecules (Vangl2, Celsr1, Prickle), Wnt11 and associated proteins (Glypican4, Fzd7, Cthrc1), Wnt5 and associated
proteins (Ror2, Cthrc1), and atypical cadherins (Dachsous, Fat). Wnt11 activates Rock (Rho-associated kinase) via Dsh and RhoA, while Wnt5
functions through JNK to activate ATF2 (activating transcription factor-2). The Wnt/Ca
2
þ
pathway (another “noncanonical” pathway) is
activated by Wnt11 or Wnt5 and triggers Ca
2
þ
signaling through CamKII (calmodulin-dependent protein kinase 2), PKC (protein kinase
“
noncanonical
”
