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Biomedical subjects

Akio Matsuda

Publications and source records attributed to Akio Matsuda.

8 recordsLinked to original sources
PubMed2005

Centaurin-alpha1 is a phosphatidylinositol 3-kinase-dependent activator of ERK1/2 mitogen-activated protein kinases.

Centaurin-alpha1 is known to be a phosphatidylinositol 3,4,5-triphosphate (PIP3)-binding protein that has two pleckstrin homology domains and a putative ADP ribosylation factor GTPase-activating protein domain. However, the physiological function of centaurin-alpha1 is still not understood. Here we have shown that transient expression of centaurin-alpha1 in COS-7 cells results in specific activation of ERK, and the activation is inhibited by co-expression of a dominant negative form of Ras. We have also found that a mutant form of centaurin-alpha1 that is unable to bind PIP3 fails to induce ERK activation and that a phosphatidylinositol 3-kinase inhibitor LY294002 inhibits centaurin-alpha1-dependent ERK activation. Furthermore, transient knockdown of centaurin-alpha1 by small interfering RNAs results in reduced ERK activation after epidermal growth factor stimulation in T-REx 293 cells. These results suggest that centaurin-alpha1 contributes to ERK activation in growth factor signaling, linking the PI3K pathway to the ERK mitogen-activated protein kinase pathway through its ability to interact with PIP3.

Adaptor Proteins, Signal Transducing↗
PubMed2004

CD45-associated protein inhibits CD45 dimerization and up-regulates its protein tyrosine phosphatase activity.

CD45, a receptor-like protein tyrosine phosphatase (PTP), plays an essential role in lymphocyte development and immune responses. Recent evidence suggests that dimerization of CD45 down-regulates its function. However, the mechanisms by which CD45 dimerization is regulated remain unclear, and there is no direct evidence that the PTP activity of CD45 dimers is less than that of monomers. CD45 in lymphocytes associates with CD45-AP (CD45-associated protein). Here we show that T cells from CD45-AP-null mice have a much higher level of CD45 dimers than those of wild-type mice, suggesting that CD45-AP inhibits CD45 dimer formation. This was confirmed with the use of a novel CD45-AP-null T-cell line, ALST-1, that we established from a spontaneous thymic tumor found in a CD45-AP-null mouse. Transfected CD45-AP inhibited CD45 dimer formation in ALST-1 cells in proportion to the amount of CD45-AP expressed. Finally, with the use of microsomal fractions from both mouse thymocytes and ALST-1 transfectants, the PTP activity of CD45 was found to be significantly lower in CD45-AP-negative cells than in CD45-AP-positive cells. Therefore, our results support a model in which binding of CD45-AP to inactive CD45 dimers converts them to active monomers.

Animals↗
PubMed2004

Homeobox protein MSX2 acts as a molecular defense mechanism for preventing ossification in ligament fibroblasts.

Ligaments and tendons are comprised of tough yet flexible connective tissue. Little is known, however, about the precise characteristics of the cells in ligaments and tendons due to the absence of specific markers and cell lines. We recently reported a periodontal ligament cell line, PDL-L2, with suppressed Runx2/Osf2 transcriptional activity and an inability to form mineralized nodules. The present study demonstrates that the homeobox protein Msx2 is a key factor in suppressing those two functions. Msx2 colocalizes with Runx2/Osf2 and suppresses its activity cooperatively, acting with another corepressor, TLE1, as a complex to recruit histone deacetylase 1 activity. Reverse transcription-PCR and in situ hybridization demonstrated that Msx2 expression is higher in periodontal ligament and tendon cells than in osteoblasts. Stable reduction of Msx2 expression in PDL-L2 cells induces osteoblastic differentiation, thereby causing matrix mineralization. Conversely, stable, forced Msx2 expression in MC3T3-E1 cells prevented osteoblast differentiation and matrix mineralization. Msx2-induced suppression of osteoblast differentiation was repressed by bone morphogenetic protein 2. In addition, Msx2 was downregulated in a symptom- and calcification-dependent manner at the affected region in patients with ossification of the posterior longitudinal ligament. Our findings indicate that Msx2 plays a central role in preventing ligaments and tendons from mineralizing.

Aged↗
PubMed2003

Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways.

We have carried out a large-scale identification and characterization of human genes that activate the NF-kappaB and MARK signaling pathways. We constructed full-length cDNA libraries using the oligo-capping method and prepared an arrayed cDNA pool consisting of 150 000 cDNAs randomly isolated from the libraries. For analysis of the NF-kappaB signaling pathway, we introduced each of the cDNAs into human embryonic kidney 293 cells and examined whether it activated the transcription of a luciferase reporter gene driven by a promoter containing the consensus NF-kappaB binding sites. In total, we identified 299 cDNAs that activate the NF-kappaB pathway, and we classified them into 83 genes, including 30 characterized activator genes of the NF-kappaB pathway, 28 genes whose involvement in the NF-kappaB pathways have not been characterized and 25 novel genes. We then carried out a similar analysis for the identification of genes that activate the MARK pathway, utilizing the same cDNA resource. We assayed 145 000 cDNAs and identified 57 genes that activate the MARK pathway. Interestingly, 27 genes were overlapping between the NF-kappaB and the MAPK pathways, which may indicate that these genes play cross-talking roles between these two pathways.

Amino Acid Sequence↗
PubMed2003

Minute carcinoma of the pancreas presenting as pancreatic pleural effusion.

A 70-year-old Japanese man with no history of pancreatitis visited his local practitioner, complaining of dyspnea on effort. Left massive pleural effusion was detected and he was then referred to our hospital. A plain chest film showed marked left pleural effusion. Thoracentesis yielded 2000 ml of bloody fluid with high amylase content (22,665 IU/l). Endoscopic retrograde pancreatography revealed a tapered occlusion of the main pancreatic duct. Pancreatic cancer was suspected, and a distal pancreatectomy and a splenectomy were performed. Histologically, the diagnosis was ductal adenocarcinoma of the pancreas, 5 x 6 mm in size, with regional lymph node metastasis. He has experienced no recurrence of cancer or pleural effusion since the operation.

Aged↗
PubMed2003

AKRL1 and AKRL2 activate the JNK pathway.

BACKGROUND: c-Jun N-terminal kinase (JNK), a member of the mitogen-activated protein kinase (MAPK) family, is activated by specific cytokines and various environmental stresses. MKK4 and MKK7 are shown to be direct activators of JNK. Although several upstream components of the JNK pathway, including members of the MAPKKK family have been described, the components lying between the receptors or sensors and JNK have not been fully characterized. RESULTS: We have identified AKRL1 and AKRL2 (Akr1p-like 1 and 2) as novel activators of the JNK pathway. AKRL1 and AKRL2 proteins have a considerable sequence similarity to Akr1p, a protein essential for endocytosis in Saccharomyces cerevisiae. Expression of AKRL1 or AKRL2 activates JNK and its activators MKK4 and MKK7. This AKRL1/2-induced JNK activation is significantly suppressed by the expression of a kinase-negative mutant of TAK1, a member of the MAPKKK family. AKRL1 and AKRL2 localize to the Golgi. Both the N-terminal half and the C-terminal transmembrane domain of AKRL1/2 are required for the JNK activation. The C-terminal transmembrane domain of AKRL1/2 is required for localization to the Golgi. CONCLUSION: AKRL1 and AKRL2 are localized to Golgi and the novel activators of the JNK pathway.

Acyltransferases↗
PubMed2002

Signet-ring cell carcinoma of the colon 7mm in size with peritonitis carcinomatosa.

A 72-year-old woman was admitted with a complaint of a sensation of abdominal fullness. Cytologic examination of ascites revealed many poorly differentiated adenocarcinoma cells. Barium enema study and colonoscopy revealed IIa+IIc-type carcinoma of the descending colon. Endoscopic mucosal resection was performed to determine the histological type and the depth of invasion. The resected tumor was 7 x 6 mm in size, and an amorphous pit pattern was observed in the depressed area by stereomicroscopy. Poorly differentiated adenocarcinoma with signet-ring cells had diffusely infiltrated into the deeper part of the submucosal layer. Immunohistochemical findings showed this tumor to have mucin derived from gastric foveolar epithelium, suggesting that the signet-ring cell carcinoma of the colon showed gastric differentiation. Primary signet-ring cell carcinoma of the colon and rectum is a rare form of adenocarcinoma of the large intestine and shows more malignant biological behavior than ordinary colorectal carcinoma. Early diagnosis and curative operation are important.

Aged↗