Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04155 (pS2)
 1,234 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The secreted proteins intestinal trefoil factor (ITF, 59 residues), pS2 (60 residues), and spasmolytic polypeptide (SP, 106 residues) form a small family of trefoil domain-containing mammalian cell motility factors, which are essential for the maintenance of all mucous-coated epithelial surfaces. We have used 1H NMR spectroscopy to determine the high-resolution structure of human ITF, which has allowed detailed structural comparisons with the other trefoil cell motility factors. The conformation of residues 10-53 of hITF is determined to high precision, but the structure of the N- and C-terrminal residues is poorly defined by the NMR data, which is probably indicative of significant mobility. The core of the trefoil domain in hITF consists of a two-stranded antiparallel beta-sheet (Cys 36 to Asp 39 and Trp 47 to Lys 50), which is capped by an irregular loop and forms a central hairpin (loop 3). The beta-sheet is preceded by a short alpha-helix (Lys 29 to Arg 34), with the majority of the remainder of the domain contained in two loops formed from His 25 to Pro 28 (loop 2) and Ala 12 to Arg 18 (loop 1), which lie on either side of the central hairpin. The region formed by the surface of loop 2, the cleft between loop 2 and loop 3, and the adjacent face of loop 3 has previously been proposed to form the functional site of trefoil domains. Detailed comparisons of the backbone conformations and surface features of the family of trefoil cell motility factors (porcine SP, pS2, and hITF) have identified significant structural and electrostatic differences in the loop 2/loop 3 regions, which suggest that each trefoil protein has a specific target or group of target molecules.
 ...
PMID:High-resolution solution structure of human intestinal trefoil factor and functional insights from detailed structural comparisons with the other members of the trefoil family of mammalian cell motility factors. 1158 54

Expression of some members of the trefoil factor (TFF) and the WNT gene families is regulated together by estrogen. We have cloned and characterized human WNT signaling molecules using bioinformatics, cDNA-library screening and cDNA-PCR to investigate expression profile of WNT signaling molecules in human gastric cancer. Here, we investigated expression profile of TFF1/pS2, TFF2/SP and TFF3/ITF in human gastric cancer. Among 7 gastric cancer cell lines, TFF1 was expressed in OKAJIMA, TMK1, MKN45, and KATO-III, TFF2 in KATO-III, and TFF3 in MKN45 and KATO-III. TFFs were preferentially expressed in diffuse-type gastric cancer cell lines. Expression of TFFs in primary gastric cancer was next investigated. TFF1 was down-regulated in 7 cases out of 12 cases (58.3%) of primary gastric cancer. TFF2 was down-regulated in 10 out of 12 cases (83.3%) of primary gastric cancer. TFF3 was down-regulated in 2 out of 12 cases (16.7%) of primary gastric cancer, and was up-regulated in 5 out of 12 cases (41.7%). TFF1 and TFF2 were frequently down-regulated in primary gastric cancer, while TFF3 was up-regulated in some cases of primary gastric cancer. This is the first report on comprehensive expression analyses on TFFs in gastric cancer.
 ...
PMID:Expression of TFF1, TFF2 and TFF3 in gastric cancer. 1216 14

TFF1/pS2, TFF2/SP and TFF3/ITF are soluble peptides with trefoil domain(s) and C-terminal dimerization domain, which are conserved among human, cow, mouse and rat. TFF1 mRNA is expressed in stomach (mucous cells in fundus and antrum), TFF2 mRNA in stomach (mucous neck cells in fundus and basal cells in antral and pyloric glands) and duodenum (Brunner's gland), TFF3 mRNA in small intestine and large intestine (goblet cells). Expression of TFF1, TFF2 and TFF3 mRNAs are differentially regulated by FGF2/bFGF, FGF7/KGF, estrogen, aspirin, arachidonic acid, X-ray irradiation, and hydrogen peroxide. Gastric cancer is classified into the intestinal type and the diffuse type. TFF mRNAs are preferentially expressed in diffuse-type gastric cancer cells. Custom-made microarray (TFF mRNAs) and ELISA (TFF proteins) might be applicable for screening methods of peritoneal and bone marrow dissemination from diffuse-type gastric cancer. TFF1 and TFF2 mRNAs are frequently down-regulated in intestinal-type gastric cancer. TFF1 gene, inactivated by deletion, missense mutation and promoter hypermethylation, is a tumor suppressor gene implicated in gastric cancer. TFF2 is a candidate tumor suppressor gene; however, genetic and epigenetic alterations of TFF2 gene in human gastric cancer remain unclear. TFF1, TFF2 and TFF3 play key roles in mucosal protection through mucous-barrier formation, and also in mucosal repair through promotion of restitution after injury. Patients with chronic atrophic gastritis and those with ulcerative colitis are at risk of gastric cancer and colorectal cancer, respectively. TFF1, TFF2 and TFF3 proteins might be applicable for chemoprevention of gastrointestinal cancer associated with chronic persistent inflammation.
 ...
PMID:Trefoil factors and human gastric cancer (review). 1279 1

Trefoil peptides (TFFs) are now considered as scatter factors, proinvasive and angiogenic agents acting through cyclooxygenase-2 (COX-2)- and thromboxane A2 receptor (TXA2-R)-dependent signaling pathways. As expression and activation levels of the epidermal growth factor receptor (EGFR) predict the metastatic potential of human colorectal cancers, the purpose of this study was to establish whether the EGF receptor tyrosine kinase (EGFR-TK) contributes to cellular invasion induced by TFFs in kidney and colonic cancer cells. Both the dominant negative form of the EGFR (HER-CD533) and the EGFR-TK inhibitor ZD1839 (Iressa) abrogated cellular invasion induced by pS2, spasmolytic polypeptide (SP) and the src oncogene, but not by ITF and the TXA2-R. Similarly, EGFR-TK inhibition by ZD1839 reversed the invasive phenotype promoted by the constitutively activated form of the EGFR (EGFRvIII) and the EGFR agonists transforming growth factor alpha (TGFalpha), amphiregulin and EGF. We also provide evidence that TFFs, EGFRvIII, and TGFalpha trigger common proinvasive pathways using the PI3'-kinase and Rho/Rho- kinase cascades. These findings identify the EGFR-TK as a key signaling element for pS2- and SP-mediated cellular invasion. It is concluded that although pS2, SP and ITF belong to the same family of inflammation- and cancer-associated regulatory peptides, they do not control identical signaling networks.
 ...
PMID:Selective abrogation of the proinvasive activity of the trefoil peptides pS2 and spasmolytic polypeptide by disruption of the EGF receptor signaling pathways in kidney and colonic cancer cells. 1288 5


<< Previous 1 2