Frizzled Signaling

Signaling through FZDs is mainly subdivided into P-catenin-dependent [36] and P-catenin-independent pathways [37]. These branches are also known as canonical and noncanonical WNT pathways, respectively. However, the terminology refers to the historical chronology of the discovery of the pathways, rather than indicating that P - catenin is the WNT- default pathway. Indeed, P-catenin signaling can be activated by other GPCRs unrelated to FZD (e.g.,

JAK2 GSK- GSK- PLK CDK Phosphorylase ABL EGFR TPK-IIB/ CSK 3alpha 3beta kinase p38Syk

TABLE 5.2 Summary of ß-Catenin-Independent FZD Signaling

Signaling Path

Cellular System

Activating WNT

Reference

WNT/cGMP/ Ca2+

Mouse F9

WNT-5A

[75]

teratocarcinoma

WNT/IPs

Mouse F9

WNT-3A (IP5)

[116]

teratocarcinoma

Osteoblasts

WNT- 3A

[117]

(murine ST2)

WNT/RAC-1

Xenopus

WNT-1

[118]

HEK293

WNT/RHO

Xenopus

WNT-1

[118]

HEK293

WNT/ROR2/CD C42

Xenopus

WNT- 5A

[41]

WNT/RAP1

Xenopus

WNT- 8

[119]

HEK293

WNT/PKA/CREB

mouse presomitic

WNT-1; WNT-3A;

[120]

mesoderm cells

WNT-7A

WNT/mTOR

Various mammalian

WNT-; WNT-3;

[121]

cells

WNT-10B

WNT/RYK

Drosophila

WNT-1; WNT-3 A

[122,123]

293T cells

Reference 38). Therefore, I will use the nomenclature P-catenin-dependent and P-catenin-independent pathways. The P-catenin-independent pathways are highly diverse [37] and are named according to the specific molecules involved in signaling (see Table 5.2). This chapter will not go into detail with planar cell polarity (PCP) signaling, referring to WNT signaling responsible for the uniform polarization and orientation of epithelial cells along the apical-basal axis as typically investigated in Drosophila [39]. In vertebrates, the lengthening and narrowing of a tissue is referred to as convergent extension regulating movement of polarized cells during embryonic development. PCP signaling and regulation of convergent extension movements are governed by PCP core proteins and multiple signaling pathways including classical players such as DVL, as well as RHO-like GTPases and JNK [39-41] -

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