Mauro L J, Olmsted E A, Skrobacz B M, Mourey R J, Davis A R, Dixon J E
Department of Biological Chemistry, University of Michigan, Ann Arbor 48109.
J Biol Chem. 1994 Dec 2;269(48):30659-67.
Absence of the tyrosine kinase activity of c-src and c-fms results in impairment of bone remodeling. Such dysfunction underscores the importance of tyrosine phosphorylation, yet the role of protein tyrosine phosphatases in bone metabolism remains unexamined. We have isolated the cDNA for a novel receptor-like tyrosine phosphatase expressed in bone and testis named osteotesticular protein tyrosine phosphatase (OST-PTP). The deduced 1711-residue protein possesses an extracellular domain with 10 fibronectin type III repeats and a cytoplasmic region with two catalytic domains. In primary rat osteoblasts, the 5.8-kilobase OST-PTP transcript is up-regulated in differentiating cultures and down-regulated in late stage mineralizing cultures. In addition, a presumed alternate transcript of 4.8-5.0 kilobases, which may lack PTP domains, is present in proliferating osteoblasts, but not detectable at other stages. Parathyroid hormone, a modulator of bone function, as well as cyclic AMP analogues, increase OST-PTP mRNA 5-8-fold in UMR 106 cells. In situ hybridization of adult rat testis revealed stage-specific expression of OST-PTP. OST-PTP may function in signaling pathways during bone remodeling, as well as serve a broader role in cell interactions associated with differentiation in bone and testis.
c-src和c-fms酪氨酸激酶活性的缺失会导致骨重塑受损。这种功能障碍突出了酪氨酸磷酸化的重要性，然而蛋白酪氨酸磷酸酶在骨代谢中的作用仍未得到研究。我们分离出了一种在骨骼和睾丸中表达的新型受体样酪氨酸磷酸酶的cDNA，命名为骨睾丸蛋白酪氨酸磷酸酶（OST-PTP）。推导的1711个残基的蛋白质具有一个含有10个纤连蛋白III型重复序列的细胞外结构域和一个含有两个催化结构域的细胞质区域。在原代大鼠成骨细胞中，5.8千碱基的OST-PTP转录本在分化培养物中上调，而在晚期矿化培养物中下调。此外，一种推测的4.8-5.0千碱基的可变转录本，可能缺乏PTP结构域，存在于增殖的成骨细胞中，但在其他阶段无法检测到。甲状旁腺激素，一种骨功能调节剂，以及环磷酸腺苷类似物，可使UMR 106细胞中的OST-PTP mRNA增加5-8倍。成年大鼠睾丸的原位杂交显示OST-PTP的阶段特异性表达。OST-PTP可能在骨重塑过程中的信号通路中发挥作用，以及在与骨骼和睾丸分化相关的细胞相互作用中发挥更广泛的作用。
