Trafficking and postsecretory events responsible for the formation of secreted human salivary peptides: A proteomics approach
Trafficking and postsecretory events responsible for the formation of secreted human salivary peptides: A proteomics approach
复制标题
DOI：
10.1074/mcp.m700501-mcp200
复制
发表时间：
2008-05-01
影响因子：
7
通讯作者：
Castagnola, Massimo
中科院分区：
文献类型：
--
作者：
Messana, Irene;Cabras, Tiziana;Castagnola, Massimo
阐明不同类型的人类唾液蛋白和肽的翻译后修饰的定位（酸性和碱性富含脯氨酸的蛋白质（PRP）、组蛋白、Statherin、P-B肽和“S型”胱抑素）对来自腮腺和下颌下腺以及腮腺、下颌下腺/舌下（Sm/SI）的富集颗粒制剂的完整蛋白质的比较反相HPLC-ESI-MS分析，并进行全唾液检测。本研究的主要结果表明：(1)所有唾液肽的磷酸化、组蛋白1的硫酸化、酸性和前体碱性PRPs的蛋白水解裂解发生在颗粒储存之前。(ii)与先前的研究一致，碱性PRP仅由腮腺分泌，而酸性PRP（aPRP）的所有同种型由腮腺和Sm/SI腺体分泌。(iii)aPRP、组胺素1和Statherin的磷酸化水平在腮腺中较高，而aPRP的裂解程度在Sm/SI腺体中较高。(iv)组胺素1酪氨酸的O-硫酸化是一种特异性的下颌下腺翻译后修饰。(v)在腮腺唾液中，组胺素3、组胺素5和组胺素6的浓度较高，但组胺素1的浓度不高。(vi)在颗粒成熟过程中，组胺素3经受第一次蛋白水解切割（产生组胺素6和5），并且在两个腺体中发生相同的相对程度。(vii)组胺素5和6的蛋白水解裂解，产生组胺素3片段的级联，发生在颗粒分泌后，并且在腮腺分泌中更广泛。（viii）碱性PRP在口腔中被未知的肽酶切割，产生各种富含脯氨酸的小肽。(ix)C-末端从他汀类药物的去除在腮腺唾液中更广泛。(x)P-B肽由两个腺体分泌，其相对量在颌下/舌下分泌中较高。(xi)与以往的研究一致，S型胱抑素主要是Sm/SI腺的产物。
To elucidate the localization of post-translational modifications of different classes of human salivary proteins and peptides (acidic and basic proline-rich proteins (PRPs), Histatins, Statherin, P-B peptide, and "S type" Cystatins) a comparative reversed phase HPLC-ESI-MS analysis on intact proteins of enriched granule preparations from parotid and submandibular glands as well as parotid, submandibular/sublingual (Sm/SI), and whole saliva was performed. The main results of this study indicate the following. (1) Phosphorylation of all salivary peptides, sulfation of Histatin 1, proteolytic cleavages of acidic and precursor basic PRPs occur before granule storage. (ii) In agreement with previous studies, basic PRPs are secreted by the parotid gland only, whereas all isoforms of acidic PRPs (aPRPs) are secreted by both parotid and Sm/SI glands. (iii) Phosphorylation levels of aPRPs, Histatin 1, and Statherin are higher in the parotid gland, whereas the extent of cleavage of aPRP is higher in Sm/SI glands. (iv) O-Sulfation of tyrosines of Histatin 1 is a posttranslational modification specific for the submandibular gland. (v) The concentration of Histatin 3, Histatin 5, and Histatin 6, but not Histatin 1, is higher in parotid saliva. (vi) Histatin 3 is submitted to the first proteolytic cleavage (generating Histatins 6 and 5) during granule maturation, and it occurs to the same relative extent in both glands. (vii) The proteolytic cleavages of Histatin 5 and 6, generating a cascade of Histatin 3 fragments, take place after granule secretion and are more extensive in parotid secretion. (viii) Basic PRPs are cleaved in the oral cavity by unknown peptidases, generating various small proline-rich peptides. (ix) C-terminal removal from Statherin is more extensive in parotid saliva. (x) P-B peptide is secreted by both glands, and its relative quantity is higher in submandibular/sublingual secretion. (xi) In agreement with previous studies, S type Cystatins are mainly the product of Sm/SI glands.