XXXX signaling pathways.

@entity1 @entity8047 @entity9702 @entity28 @entity4357 @entity21944 @entity584 @entity4016 @entity2124 @entity10240 @entity4149 @entity18481 @entity1366 @entity9045
UNASSIGNED: Over 20years ago, our laboratory showed that @entity2124 ( @entity2124 ) signals through the @entity9045 -associated @entity4149 kinase @entity4016 . We showed that @entity2124 binding to its membrane-bound receptor enhances binding of @entity4016 to the @entity9045 , activates @entity4016 , and stimulates @entity18481 phosphorylation of both @entity4016 and @entity9045 . The activated @entity4016 / @entity9045 complex recruits a variety of signaling proteins, thereby initiating multiple signaling pathways and cellular responses. These proteins and pathways include: 1) Stat transcription factors implicated in the expression of multiple genes, including the gene encoding insulin-like growth factor 1; 2) Shc adapter proteins that lead to activation of the @entity10240 -SOS-Ras-Raf- @entity8047 - @entity1366 pathway; 3) insulin receptor substrate proteins implicated in the @entity4357 -3-kinase and @entity584 pathway; 4) signal regulatory protein a, a transmembrane scaffold protein that recruits proteins including the @entity4149 phosphatase @entity9702 ) @entity21944 , a scaffold protein that can activate @entity4016 and enhance @entity2124 regulation of the actin cytoskeleton. Our recent work has focused on the function of @entity21944 . We have shown that SH2B1b is recruited to and phosphorylated by @entity4016 in response to @entity2124 . @entity21944 localizes to the plasma membrane, cytoplasm and focal adhesions; it also cycles through the nucleus. @entity21944 regulates the actin cytoskeleton and promotes @entity2124 -dependent motility of RAW264.7 macrophages. Mutations in @entity21944 have been found in @entity1 exhibiting severe early-onset @entity28 and insulin resistance. These mutations impair @entity21944 enhancement of @entity2124 -induced macrophage motility. As @entity21944 is expressed ubiquitously and is also recruited to a variety of receptor @entity4149 kinases, our results raise the possibility that effects of @entity21944 on the actin cytoskeleton in various cell types, including neurons, may play a role in regulating body weight.
