1. Noncanonical Wnt Signaling through G Protein-Linked PKC  Activation Promotes Bone Formation Xiaolin et al. Dev cell. (2007)

2. Christine Hartmann. Trends cell biol. (2006) Formation of the skeleton through intramembranous and endochondral ossification Intramembranous ossification Endochondral ossification

3. Christine Hartmann. Trends cell biol. (2006) Role of canonical Wnt-  -cat signaling during lineage differentiation and maturation of osteoblasts

4. Skeletal defects caused by mutations with regard to components of the canonical Wnt pathway Christine Hartmann. Trends cell biol. (2006)

5. Malbon CC. Nat Rev Mol Cell Biol. 2005. Rhee SG. Annu Rev Biochem. 2001. G-protein signaling and PLC mediated PKC activation Classic PKC (cPKC) : ,  1,  2,  → activated by DAG, phosphatidylserine and Ca 2+ Novel PKC (nPKC) : , , ,  → activated by DAG and phosphatidylserine Atypical PKC (aPKC) :, ,  → activated by phosphatidylserine

6. Sheldahl et al. Curr Biol. (1999) Sheldahl et al. J Cell Biol. (2003) Wnts activate PKC through G-protein signal Penzo-Mendez et al. Dev Biol. (2003)

7. Wnt3a induces osteoblast differentiation and MARCKS phosphorylation via PKC  in ST2 cells Wnt3a nPKC osteoblastogenesis

8. PKC  Is Required for Wnt3a-Induced Osteoblastogenesis, but Not for Canonical Wnt Signaling in ST2 Cells PKC cPKCCa 2+ nPKC(  ) aPKC : PKC  pseudosubstrate PKC  pseudosubstrate

9. Rottlerin Inhibits Wnt3a-Induced Osteoblast Differentiation in ST2 Cells Wnt3a PKC  osteoblastogenesis  -cat

10. PKC  Activation via Gq Signaling Promotes Wnt3a-Induced Osteoblastogenesis and Requires Dvl in ST2 Cells Pertussis toxin : Gi-G  inhibitor Gq family : Gq, G 11, G 14/15/16 Wnt3a PKC  osteoblastogenesis  -cat Dvl GqGq PLC

11. PKC  Activation by Wnt3a Correlates with Dvl-2 Translocation to the Plasma Membrane and Is Insensitive to Dkk1 in ST2Cells

12. Wnt3a Induces Colocalization of PKCδ and Dvl-1,3 at the Plasma Membrane in ST2 Cells

13. Removal of PKC  Results in a Deficit in Embryonic Bone Formation

14. Wnt7b Induces Osteoblastogenesis and PKC  Activity, but Does Not Activate Canonical Wnt Signaling

15. Removal of Wnt7b in Skeletal Cells Results in Defects in Bone Formation

16. α β LRP γ Wnt Dvl FZ PLC PKC  ?? Osteoblastogenesis  -cat Model for Wnt-PKC  signaling promotes bone formation