Wnt/Ca+ pathway


Pathway Description

Wnt glycolipoproteins are extracellular ligands that can be found in many species, ranging from the sea anemone to human. Wnts are signaling factors regulating several key developmental processes, such as proliferation, differentiation, asymmetric division, patterning and cell fate determination.The non-canonical Wnt/Ca2+ signaling cascade is less characterized than their canonical counterpart, the Wnt/β-catenin pathway. The Wnt/Ca2+ signaling pathway was deciphered as a crucial mediator in development. However, now there is substantial evidence that the signaling cascade is involved in many other molecular phenomena.

There is crosstalk between the non-canonical Wnt/Ca2+ signaling and canonical Wnt β-catenin signaling pathway. These pathways are not autonomous, their boundaries are not stringent and there are considerable degrees of overlapping between them.

Wnt/Fz ligand receptor interacts with participating co-receptor Ror1/2 activating PLC. A tri-protein complex of Dvl-axin-GSK is formed, Cn and CamKII are activated which in turn activate NFAT and NFκB. DAG is activated by released calcium from ER, which activates PKC. PKC activates NFκB and CREB. NFAT, NFκB, and CREB translocate to the nucleus and transcribe downstream regulatory genes. Wnt/Fz receptor-ligand interaction may activate phosphodiesterase 6 (PDE6) in a calcium-dependent manner, leading to a decrease in cyclic guanosine monophosphate (cGMP).