M-CSF SIGNALING IN OSTEOCLAST FORMATION AND FUNCTION

描述(改编自调查者摘要)：区分 破骨细胞(OCS)依赖于两个分子提供的关键信号： 骨保护素(OPGL)和巨噬细胞集落刺激因子(M-CSF)。这个 巨噬细胞集落刺激因子与其受体(c-FMS)结合导致酪氨酸磷酸化 在受体的细胞质部分的残基，产生下游 信号。虽然已经对c-fms进行了结构和功能的分析 此前，在其他类型的细胞中，这些研究得出了相互矛盾的结果。 此外，还有一个问题是，用其他细胞类型获得的结果 可以外推到OCS中的c-FMS信令。因此，这项提议将 确定对破骨细胞(OC)存活至关重要的酪氨酸残基， 成骨细胞前体细胞的增殖分化及成熟细胞的功能 OCS。

DESCRIPTION (adapted from the Investigator's abstract): The differentiation of osteoclasts (OCs) is dependent upon critical signals provided by two molecules: osteoprotegerin (OPGL) and macrophage colony stimulating factor (M-CSF). The binding of M-CSF to its receptor (c-fms) results in phosphorylation of tyrosine residues in the cytoplasmic portion of the receptor, generating downstream signals. Although structure-function analyses of c-fms have been carried out previously in other cell types, these studies have yielded conflicting results. In addition, there is question whether results obtained with other cell types can be extrapolated to c-fms signaling in OCs. This proposal will therefore determine the tyrosine residues critical for osteoclast (OC) survival, proliferation and differentiation of OC precursors, and the function of mature OCs.