Galectin-3 is a substrate for prostate specific antigen (PSA) in human seminal plasma.
Galectin-3 is a substrate for prostate specific antigen (PSA) in human seminal plasma.
复制标题
DOI：
10.1002/pros.21236
复制
发表时间：
2011-02-01
期刊：
影响因子：
2.8
通讯作者：
Diekman, Alan B.
中科院分区：
文献类型：
--
作者：
Saraswati, Sarika;Block, Ashley S.;Davidson, Mari. K.;Rank, Roger G.;Mahadevan, Maha;Diekman, Alan B.
半乳糖凝集素-3是一种多价碳水化合物结合蛋白，参与细胞粘附、细胞周期控制、免疫调节和癌症进展，包括前列腺癌。半乳糖凝集素-3的功能受蛋白水解切割的调节，蛋白水解切割破坏半乳糖凝集素-3的多价性，同时保留碳水化合物结合活性。在人类精液中，半乳糖凝集素-3存在于精浆中，并且还与前列腺体（前列腺分泌的外泌体样囊泡）相关。在目前的研究中，我们的特点是蛋白水解活性，切割半乳糖凝集素-3人精浆。开发了一种体外试验来研究精浆中半乳糖凝集素-3的切割。测定了蛋白酶抑制剂、二价离子螯合剂和Zn 2+对切割活性的影响。测试从精浆富集的蛋白酶切割半乳糖凝集素-3的能力。亲和纯化和微序列分析用于鉴定半乳糖凝集素-3中的切割位点。半乳糖凝集素-3在人精浆中以完整和截短形式被鉴定。从精浆中富集的明胶酶不裂解半乳糖凝集素-3。抑制剂研究表明，精浆中的半乳糖凝集素-3切割活性是Zn 2+敏感的丝氨酸蛋白酶。前列腺特异性抗原（PSA）被证明可以在酪氨酸107-甘氨酸108之间切割半乳糖凝集素-3，并产生功能活性的单价凝集素。PSA是由前列腺上皮分泌的胰凝乳蛋白酶样丝氨酸蛋白酶，通常在射精后液化精液中起作用。此外，PSA通过其在免疫调节、侵袭和凋亡中的作用而参与促进局限性前列腺肿瘤和骨转移。我们的研究结果表明，PSA调节人精液中的半乳糖凝集素-3，并可能在前列腺癌进展过程中调节半乳糖凝集素-3的功能。
Galectin-3 is a multivalent carbohydrate-binding protein involved in cell adhesion, cell cycle control, immunomodulation, and cancer progression, including prostate cancer. Galectin-3 function is regulated by proteolytic cleavage that destroys galectin-3 multivalency while preserving carbohydrate-binding activity. In human semen, galectin-3 is present in seminal plasma and is also associated with prostasomes, exosome-like vesicles secreted by the prostate. In the current study, we characterized the proteolytic activity that cleaves galectin-3 in human seminal plasma. An in vitro assay was developed to investigate galectin-3 cleavage in seminal plasma. The effect of protease inhibitors, divalent ion chelators, and Zn2+ on the cleavage activity was determined. Proteases enriched from seminal plasma were tested for their ability to cleave galectin-3. Affinity purification and microsequence analysis were used to identify the cleavage site in galectin-3. Galectin-3 was identified in human seminal plasma in an intact and truncated form. Gelatinases enriched from seminal plasma did not cleave galectin-3. Inhibitor studies indicated that the galectin-3 cleavage activity in seminal plasma is a Zn2+ sensitive, serine protease. Prostate specific antigen (PSA) was demonstrated to cleave galectin-3 between tyrosine107-glycine108 and produce a functionally-active, monovalent lectin. PSA is a chymotrypsin-like serine protease secreted by the prostatic epithelium and normally functions in liquefaction of semen following ejaculation. Furthermore, PSA is implicated in the promotion of localized prostate tumors and bone metastases by its roles in immunomodulation, invasion, and apoptosis. Our results indicate that PSA regulates galectin-3 in human semen and may regulate galectin-3 function during prostate cancer progression.
登录
查看更多内容
影响因子：
3
作者：
Ochieng, J;Furtak, V;Lukyanov, P
通讯作者：
Lukyanov, P
影响因子：
27.4
作者：
Guévremont, M;Martel-Pelletier, J;Reboul, P
通讯作者：
Reboul, P
影响因子：
--
作者：
Ellerhorst, J;Troncoso, P;Lotan, R
通讯作者：
Lotan, R
甲状腺素在感染中的作用。
DOI：
10.1038/nrmicro2146
发表时间：
2009-06
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1073/pnas.90.8.3466
发表时间：
1993-04-15
影响因子：
11.1
作者：
LOTZ, MM;ANDREWS, CW;MERCURIO, AM
通讯作者：
MERCURIO, AM