FIGURE 4.

Model for IGF-1R/integrin interactions in bone cells. IGF-1R forms a complex with αvβ3 integrin that is required for IGF-1 activation of IGF-1R. Mechanical load increases whereas unloading decreases formation of this complex and thus regulates IGF-1 responsiveness. Formation of the integrin/IGFIR complex brings to IGF-1R, non-receptor kinases such as FAK family and src family kinases that are hypothesized to activate IGF-1R independently and/or synergistically with IGF-1. Caveolin may also contribute to the formation of an integrin/IGF-1R complex. SHPS-1/SHP-2 has been shown to play a role in regulating IGF-1 signaling in some tissues, but this role in bone cells is unclear. IGF-1R signals through two main pathways involving Akt and Ras/Raf/MEK/ERK, respectively. Akt, by phosphorylating BAD, has an anti-apoptotic effect, while ERK promotes proliferation. However, these represent just two of a number of intracellular events triggered by the activated IGF-1R.