Fam198a, a member of secreted kinase, secrets through caveolae biogenesis pathway  

作　　者：Zhuang Wei Tao Liu Jigang Lei Yuan Wu Shilong Wang Kan Liao 

机构地区：[1]Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China [2]CAS Center for Excellence in Molecular Ceil Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China [3]School of Life Science and Technology, Tongji University, Shanghai 200092, China

出　　处：《Acta Biochimica et Biophysica Sinica》2018年第10期968-975,共8页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the grants from the National Natura Science Foundation of China （Nos, 31370818 and 31701165）.

摘　　要：Fam198a is a member of four-jointed protein kinases, a secreted protein kinase family. It was identified as a caveolae-associated protein and colocalized with cavin-1 and caveolin-1 in both tissues and cells. The newly synthesized Fam198a precursor in endoplasmic reticulum （ER） was transported by caveolae biogenesis vesicles to Golgi apparatus in which it was proteolytically cleaved into the secreted mature form. The amino acid mutation analysis identified Arg 120 and 437 as the proteolytic sites in Fam198a precursor during maturation. In mouse embryo fibroblasts （MEFs） obtained from cavin-1^-/- or caveolin-1^-/- mice, Fam198a precursor was retained in ER and no mature Fam198a could be formed in these cells. Ectopic expression of exogenous cavin-1 in cavin-1^-/- MEFs restored the blocked Fam198a post-translational process and secretion. Cavin-1 was also required for Fam198a secretion after its maturation in Golgi apparatus. Ectopic expression of cavin-1 in A549 cells restored the blocked Fam198a secretion. These results suggest that protein secretion is an important function for caveolae biogenesis pathway and the disruption of caveolae system will affect those functions played by the secreted proteins.Fam198a is a member of four-jointed protein kinases, a secreted protein kinase family. It was identified as a caveolae-associated protein and colocalized with cavin-1 and caveolin-1 in both tissues and cells. The newly synthesized Fam198a precursor in endoplasmic reticulum （ER） was transported by caveolae biogenesis vesicles to Golgi apparatus in which it was proteolytically cleaved into the secreted mature form. The amino acid mutation analysis identified Arg 120 and 437 as the proteolytic sites in Fam198a precursor during maturation. In mouse embryo fibroblasts （MEFs） obtained from cavin-1^-/- or caveolin-1^-/- mice, Fam198a precursor was retained in ER and no mature Fam198a could be formed in these cells. Ectopic expression of exogenous cavin-1 in cavin-1^-/- MEFs restored the blocked Fam198a post-translational process and secretion. Cavin-1 was also required for Fam198a secretion after its maturation in Golgi apparatus. Ectopic expression of cavin-1 in A549 cells restored the blocked Fam198a secretion. These results suggest that protein secretion is an important function for caveolae biogenesis pathway and the disruption of caveolae system will affect those functions played by the secreted proteins.

关 键 词：Fam198a CAVEOLAE cavin-1 protein processing 

分 类 号：Q-0[生物学] S436.612.2[农业科学—农业昆虫与害虫防治]