Regulation of scu-PA secretion and u-PA Receptor Expression in Osteoblast-Iike Cells

Cell Structure and Function

Osamu Matsuo¹  Tohgo Nonaka¹  Hideharu Fukao¹  Kiyotaka Okada¹  Hiraku Kikuchi²  Shigeru Ueshima²  Seisuke Tanaka² 

[1] The Departments of Physiology, Kinki University of Medicine;Orthopaedic Surgery, Kinki University of Medicine

关键词: urokinase-type plasminogen activator (u-PA);    u-PA receptor;    osteoblast;    cyclic AMP (cAMP);    protein kinase C (PKC);   

DOI  :  10.1247/csf.18.355

学科分类：分子生物学，细胞生物学和基因

来源: Japan Society for Cell Biology

【 摘 要 】

References(43)Cited-By(2)The production of proteolytic emzymes by osteoblasts is considered important for initiating osteoclastic bone resorption. Using the established cell line NY as an example of osteoblast-like cells, the effect of intracellular cyclic AMP (cAMP) and protein kinase C (PKC) on plasminogen activator secretion and its specific binding to the cells were investigated. HT-1080 cells were used as the control. NY cells predominantly secrete single-chain urokinase-type plasminogen activator (scu-PA) and some two-chain u-PA. Both scu-PA and u-PA were present in the cell surface and cell lysate of NY cells, and their distribution in HT-1080 cells was quite similar to that of NY cells. Exposing cells to phorboi myristate acetate (PMA) or dibutyryl cyclic AMP (db cAMP) enhanced the secretion of scu-PA and two-chain u-PA, whereas 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7) decreased scu-PA secretion, indicating that it is enhanced by protein kinase C (PKC) as well as by cAMP in NY cells. On the other hand, in HT-1080 cells, PMA decreased the level of two-chain u-PA secretion into the conditioned medium. The binding assay of 125I-DFP-u-PA to NY cells revealed the presence of a single class of binding sites with a Kd of 2.23 nM and Bmax of 0.82×106 binding sites/cell. PMA however, altered neither the Kd nor the Bmax. Dibutyryl cAMP increased the Bmax 1.9 fold. Thus, NY cells secrete u-PA and express specific binding sites on the cell surface, which are modulated by cAMP and PKC. The u-PA/u-PA receptor system may contribute to osteoblastic bone resorption.

【 授权许可】

Unknown