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Publication : GRP94 is essential for mesoderm induction and muscle development because it regulates insulin-like growth factor secretion.

First Author  Wanderling S Year  2007
Journal  Mol Biol Cell Volume  18
Issue  10 Pages  3764-75
PubMed ID  17634284 Mgi Jnum  J:146397
Mgi Id  MGI:3837519 Doi  10.1091/mbc.E07-03-0275
Citation  Wanderling S, et al. (2007) GRP94 is essential for mesoderm induction and muscle development because it regulates insulin-like growth factor secretion. Mol Biol Cell 18(10):3764-75
abstractText  Because only few of its client proteins are known, the physiological roles of the endoplasmic reticulum chaperone glucose-regulated protein 94 (GRP94) are poorly understood. Using targeted disruption of the murine GRP94 gene, we show that it has essential functions in embryonic development. grp94-/- embryos die on day 7 of gestation, fail to develop mesoderm, primitive streak, or proamniotic cavity. grp94-/- ES cells grow in culture and are capable of differentiation into cells representing all three germ layers. However, these cells do not differentiate into cardiac, smooth, or skeletal muscle. Differentiation cultures of mutant ES cells are deficient in secretion of insulin-like growth factor II and their defect can be complemented with exogenous insulin-like growth factors I or II. The data identify insulin-like growth factor II as one developmentally important protein whose production depends on the activity of GRP94.
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