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10.1074/jbc.M115.693598

http://scihub22266oqcxt.onion/10.1074/jbc.M115.693598
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C4825016!4825016!26865633
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suck abstract from ncbi


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pmid26865633      J+Biol+Chem 2016 ; 291 (15): 8140-9
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  • Regulation of Ligand and Shear Stress-induced Insulin-like Growth Factor 1 (IGF1) Signaling by the Integrin Pathway* #MMPMID26865633
  • Tahimic CGT; Long RK; Kubota T; Sun MY; Elalieh H; Fong C; Menendez AT; Wang Y; Vilardaga JP; Bikle DD
  • J Biol Chem 2016[Apr]; 291 (15): 8140-9 PMID26865633show ga
  • Mechanical loading of the skeleton, as achieved during daily movement and exercise, preserves bone mass and stimulates bone formation, whereas skeletal unloading from prolonged immobilization leads to bone loss. A functional interplay between the insulin-like growth factor 1 receptor (IGF1R), a major player in skeletal development, and integrins, mechanosensors, is thought to regulate the anabolic response of osteogenic cells to mechanical load. The mechanistic basis for this cross-talk is unclear. Here we report that integrin signaling regulates activation of IGF1R and downstream targets in response to both IGF1 and a mechanical stimulus. In addition, integrins potentiate responsiveness of IGF1R to IGF1 and mechanical forces. We demonstrate that integrin-associated kinases, Rous sarcoma oncogene (SRC) and focal adhesion kinase (FAK), display distinct actions on IGF1 signaling; FAK regulates IGF1R activation and its downstream effectors, AKT and ERK, whereas SRC controls signaling downstream of IGF1R. These findings linked to our observation that IGF1 assembles the formation of a heterocomplex between IGF1R and integrin ?3 subunit indicate that the regulation of IGF1 signaling by integrins proceeds by direct receptor-receptor interaction as a possible means to translate biomechanical forces into osteoanabolic signals.
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