Cyclic GMP and protein kinase G control a Src-containing mechanosome in osteoblasts.

ABSTRACT: Mechanical stimulation is crucial for bone growth and remodeling, and fluid shear stress promotes anabolic responses in osteoblasts through multiple second messengers, including nitric oxide (NO). NO triggers production of cyclic guanosine 3',5'-monophosphate (cGMP), which in turn activates protein kinase G (PKG). We found that the NO-cGMP-PKG signaling pathway activates Src in mechanically stimulated osteoblasts to initiate a proliferative response. PKGII was necessary for Src activation, a process that also required the interaction of Src with β₃ integrins and dephosphorylation of Src by a complex containing the phosphatases SHP-1 (Src homology 2 domain-containing tyrosine phosphatase 1) and SHP-2. PKGII directly phosphorylated and stimulated SHP-1 activity, and fluid shear stress trigge

SUBMITTER: Rangaswami H 

PROVIDER: S-EPMC3093297 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature