Wnt Signaling

Wnt proteins are secreted glycoproteins that regulate diverse developmental processes such as differentiation, cell migration and proliferation during embryogenesis and in adult tissues. Dysregulation of Wnt signaling is known to promote tumorigenesis and metastasis.

Targets
Literature
Pathways
Receptor Data

The Wnt/β-catenin (canonical) pathway is well-characterized. In the absence of a Wnt protein, cytoplasmic β-catenin levels are kept low by the 'destruction complex', which is composed of adenomatous polyposis coli (APC), axin and glycogen synthase kinase 3 (GSK-3). The destruction complex mediates β-catenin phosphorylation, which tags it for ubiquitination and proteasomal degradation. Wnt proteins bind to Frizzled receptors and LRP co-receptors, which causes activation of Dishevelled family proteins. Dishevelled inhibits the destruction complex leading to an accumulation of cytoplasmic β-catenin. β-catenin translocates to the nucleus where it interacts with transcription factors of the TCF/LEF family and promotes gene expression.

There are two further Wnt signaling pathways. Wnt proteins can stimulate release of intracellular calcium and activate calcium-sensitive enzymes such as PKC, CaMKII and calcineurin. In addition, the Wnt/Calcium pathway has been linked to activation of nemo-like kinase, which phosphorylates TCF transcription factors and inhibits Wnt/β-catenin signaling. The planar cell polarity pathway regulates the polarity of epithelial cells within the plane of an epithelium and involves activation of Rho GTPases, JNK and Rho kinases.

Wnt signaling can be modified by an array of other proteins, for example Sclerostin can bind to LRP co-receptors and inhibit this pathway. Furthermore, CK1 has been suggested to phosphorylate the cytoplasmic domain of LRP to regulate signaling and protein phosphatases have a role in determining the disassembly of the destruction complex.

Literature for Wnt Signaling

Cancer

Cancer Research Product Guide

A collection of over 750 products for cancer research, the guide includes research tools for the study of:

  • Cancer Metabolism
  • Epigenetics in Cancer
  • Receptor Signaling
  • Cell Cycle and DNA Damage Repair
  • Angiogenesis
  • Invasion and Metastasis
Kinases

Kinases Product Listing

A collection of over 400 products for kinase research, the listing includes inhibitors of:

  • Receptor Tyrosine Kinases
  • Protein Kinases A, C, D and G
  • PI-3 Kinase, Akt and mTOR
  • MAPK Signaling
  • Receptor Serine/Threonine Kinases
Stem Cells

Stem Cells Scientific Review

Written by Kirsty E. Clarke, Victoria B. Christie, Andy Whiting and Stefan A. Przyborski, this review provides an overview of the use of small molecules in the control of stem cell growth and differentiation. Key signaling pathways are highlighted, and the regulation of ES cell self-renewal and somatic cell reprogramming is discussed. Compounds available from Tocris are listed.

Pathways for Wnt Signaling

Wnt

Wnt Signaling Pathway

The Wnt pathway is involved in cellular differentiation and proliferation in adult tissues and also during embryogenesis. Disturbances within the pathway may lead to the formation of tumors and promote metastasis.

Wnt Gene Data

Gene Species Gene Symbol Gene Accession No. Protein Accession No.
Wnt1 Human WNT1 NM_005430 P04628
Mouse Wnt1 NM_021279 P04426
Rat Wnt1 NM_001105714 XP_235639
Wnt2 Human WNT2 NM_003391 P09544
Mouse Wnt2 NM_023653 P21552
Rat Wnt2 XM_575397 Q2IBD1
Wnt2B Human WNT2B NM_004185 Q93097
Mouse Wnt2b NM_009520 O70283
Rat Wnt2b XM_342308 Q9QXK5
Wnt3 Human WNT3 NM_030753 P56703
Mouse Wnt3 NM_009521 P17553
Rat Wnt3 NM_001105715 XP_221016
Wnt3A Human WNT3A NM_033131 P56704
Mouse Wnt3a NM_009522 P27467
Rat Wnt3a NM_001107005 XP_220546
Wnt4 Human WNT4 NM_030761 P56705
Mouse Wnt4 NM_009523 P22724
Rat Wnt4 NM_053402 Q4G052
Wnt5A Human WNT5A NM_003392 P41221
Mouse Wnt5a NM_009524 P22725
Rat Wnt5a NM_022631 Q14UC9
Wnt5B Human WNT5B NM_030775 Q9H1J7
Mouse Wnt5b NM_009525 P22726
Rat Wnt5b NM_001100489 Q8CFB3
Wnt6 Human WNT6 NM_006522 Q9Y6F9
Mouse Wnt6 NM_009526 P22727
Rat Wnt6 NM_001108226 XP_237295
Wnt7A Human WNT7A NM_004625 O00755
Mouse Wnt7a NM_009527 P24383
Rat Wnt7a XM_342723 Q8CFB1
Wnt7B Human WNT7B NM_058238 P56706
Mouse Wnt7b NM_009528 P28047
Rat Wnt7b NM_001009695 Q5NSW6
Wnt8A Human WNT8A NM_058244 Q9H1J5
Mouse Wnt8a NM_009290 Q64527
Rat Wnt8a NM_001106155 XP_226051
Wnt8B Human WNT8B NM_003393 Q93098
Mouse Wnt8b NM_011720 Q9WUD6
Rat Wnt8b NM_001106359 XP_219959
Wnt9A Human WNT9A NM_003395 O14904
Mouse Wnt9a NM_139298 Q8R5M2
Rat Wnt9a NM_001105783 XP_220556
Wnt9B Human WNT9B NM_003396 O14905
Mouse Wnt9b NM_011719 O35468
Rat Wnt9b NM_001107055 XP_221015
Wnt10A Human WNT10A NM_025216 Q9GZT5
Mouse Wnt10a NM_009518 P70701
Rat Wnt10a NM_001108227 XP_237296
Wnt10B Human WNT10B NM_003394 O00744
Mouse Wnt10b NM_011718 P48614
Rat Wnt10b NM_001108111 XP_235636
Wnt11 Human WNT11 NM_004626 O96014
Mouse Wnt11 NM_009519 P48615
Rat Wnt11 XM_238122 Q91WY1
Wnt16 Human WNT16 NM_057168 Q9UBV4
Mouse Wnt16 NM_053116 Q9QYS1
Rat Wnt16 NM_001109223 XP_575403