Biomedical subjects

Hitoshi Yoshida

Publications and source records attributed to Hitoshi Yoshida.

At least 37 records · Page 2Linked to original sources

PubMed2004

Regulation of ethylene gas biosynthesis by the Arabidopsis ETO1 protein.

Ethylene gas is used as a hormone by plants, in which it acts as a critical growth regulator. Its synthesis is also rapidly evoked in response to a variety of biotic and abiotic stresses. The Arabidopsis ethylene-overproducer mutants eto2 and eto3 have previously been identified as having mutations in two genes, ACS5 and ACS9, respectively; these encode isozymes of 1-aminocyclopropane-1-carboxylic acid synthase (ACS), which catalyse the rate-limiting step in ethylene biosynthesis. Here we report that another ethylene-overproducer mutation, eto1, is in a gene that negatively regulates ACS activity and ethylene production. The ETO1 protein directly interacts with and inhibits the enzyme activity of full-length ACS5 but not of a truncated form of the enzyme, resulting in a marked accumulation of ACS5 protein and ethylene. Overexpression of ETO1 inhibited induction of ethylene production by the plant growth regulator cytokinin, and promoted ACS5 degradation by a proteasome-dependent pathway. ETO1 also interacts with CUL3, a constituent of ubiquitin ligase complexes in which we propose that ETO1 serves as a substrate-specific adaptor protein. ETO1 thus has a dual mechanism, inhibiting ACS enzyme activity and targeting it for protein degradation. This permits rapid modulation of the concentration of ethylene.

Amino Acid Motifs↗

PubMed2004

Receptor-operated Ca2+ influx and its association with the Src family in secretagogue-stimulated pancreatic acini.

We investigated signal transduction between receptor-operated Ca(2+) influx (ROCI) and Src-related nonreceptor protein tyrosine kinase (PTK) in rat pancreatic acini. CCK and the Ca(2+) ionophore enhanced the Src-related PTK activity, whereas the high-affinity CCK-A receptor agonists, fibroblast growth factor (FGF), and the protein kinase C (PKC) activator had no or little effect. This increase was abolished by eliminating [Ca(2+)](o), loading of the intracellular Ca(2+) chelator, and administering the PTK inhibitor genistein. While genistein inhibited extracellular Ca(2+) or Mn(2+) entry induced by CCK and carbachol, it did not affect intracellular Ca(2+) release and oscillations. CCK dose-dependently increased the Src phosphotransferase activity, which was abolished by inhibitors of G(q) protein, phospholipase C (PLC), and Src, but not by the calmodulin kinase (CaMK) inhibitor. Intensities of the Src band and amounts of tyrosine phosphorylated Src were enhanced by CCK stimulation. Thus, Src cascades appear to be coupled to the low-affinity CCK-A receptor and utilize G(q)-PLC pathways for their activation, independent of PKC and CaMK cascades. The low-affinity CCK-A receptor regulates ROCI via mediation of Src-related PTK and activates Src pathways to cause [Ca(2+)](o)-dependent pancreatic exocytosis.

Amylases↗

PubMed2004

Complement C1q regulates LPS-induced cytokine production in bone marrow-derived dendritic cells.

We show here that C1q suppresses IL-12p40 production in LPS-stimulated murine bone marrow-derived dendritic cells (BMDC). Serum IL-12p40 concentration of C1q-deficient mice was higher than that of wild-type mice after intraperitoneal LPS-injection. Because neither globular head of C1q (gC1q) nor collagen-like region of C1q (cC1q) failed to suppress LPS-induced IL-12p40 production, both gC1q and cC1q, and/or some specialized conformation of native C1q may be required for the inhibition. While C1q did not affect mRNA expression of Toll-like receptor 4 (TLR4), MD-2, and myeloid differentiation factor 88 (MyD88), BMDC treated with C1q showed the reduced activity of NF-kappaB and the delayed phosphorylation of p38, c-Jun N-terminal kinase, and extracellular signal-regulated kinase after LPS-stimulation. CpG oligodeoxynucleotide-induced IL-12p40 and TNF-alpha production, another MyD88-dependent TLR-mediated signal, was also suppressed by C1q treatment. Therefore, C1q is likely to suppress MyD88-dependent pathway in TLR-mediated signals. In contrast, C1q failed to suppress colony formation of B cells responding to LPS or LPS-induced CD40 and CD86 expression on BMDC in MyD88-deficient mice, indicating that inhibitory effects of C1q on MyD88-independent pathways may be limited. Taken together, C1q may regulate innate and adaptive immune systems via modification of signals mediated by interactions between invading pathogens and TLR.

Adaptor Proteins, Signal Transducing↗

PubMed2004

A role of OsGA20ox1 , encoding an isoform of gibberellin 20-oxidase, for regulation of plant stature in rice.

Gibberellin (GA) 20-oxidase (GA20ox) is a key enzyme that normally catalyzes the penultimate steps in GA biosynthesis. One of the GA20ox genes in rice (Oryza sativa L.), OsGA20ox2 ( SD1 ), is well known as the "Green Revolution gene", and loss-of function mutation in this locus causes semi-dwarfism. Another GA20ox gene, OsGA20ox1, has also been identified, but its contribution to plant stature has remained unclear because no suitable mutants have been available. We isolated a mutant, B142, tagged with a T-DNA containing three CaMV 35S promoters, which showed a tall, GA-overproduction phenotype. The final stature of the B142 mutant reflects internode overgrowth and is approximately twice that of its wild-type parent. This mutant responds to application of both GA3 and a GA biosynthesis inhibitor, indicating that it is a novel tall mutant of rice distinct from GA signaling mutants such as slr1 . The integrated T-DNAs, which contain three CaMV 35S promoters, are located upstream of the OsGA20ox1 open reading frame (ORF) in the B142 mutant genome. Analysis of mRNA and the endogenous GAs reveal that biologically active GA level is increased by up-regulation of the OsGA20ox1 gene in B142. Introduction of OsGA20ox1 cDNA driven by 35S promoter into the wild type phenocopies the morphological characteristics of B142. These results indicate that the elongated phenotype of the B142 mutant is caused by up-regulation of the OsGA20ox1 gene. Moreover, the final stature of rice was reduced by specific suppression of the OsGA20ox1 gene expression. This result indicates that not only OsGA20ox2 but also OsGA20ox1 affects plant stature.

Binding Sites↗

PubMed2004

Interleukin-8 promotes non-rapid eye movement sleep in rabbits and rats.

Interleukin-8 (IL-8) is a cytokine found in the brain. In this study, the ability of IL-8 to induce sleep in rabbits and rats was investigated. Twenty-seven Sprague-Dawley rats and 16 male New Zealand White rabbits were provided electroencephalographic (EEG) electrodes, a brain thermistor, and a lateral intracerebroventricular cannula. The animals were injected intracerebroventricularly (i.c.v.) with pyrogen-free saline and, one of the following doses of IL-8 on a separate day: 1.25 or 12.5 ng in rabbits and 10, 50, or 100 ng in rats. EEG, brain temperature, and motor activity were recorded for 23 h after the i.c.v. injections. IL-8 increased time spent in non-rapid eye movement sleep (NREMS) without affecting rapid eye movement sleep (REMS). In rabbits, both doses of IL-8 promoted NREMS. In rats, the 10 and 50 ng doses of IL-8 failed to affect sleep, but the 100 ng dose of IL-8 enhanced NREMS. EEG slow-wave activity during NREMS was increased after the high dose of IL-8 in rabbits. IL-8 also induced fever in rabbits but not rats. Heat inactivated IL-8 did not alter any of the parameters measured. Current results support the notion that the brain cytokine network plays a role in sleep regulation.

Animals↗

PubMed2003

Distinct regulators for Plk1 activation in starfish meiotic and early embryonic cycles.

The Polo-like kinase, Plk, has multiple roles in regulating mitosis. In particular, Plk1 has been postulated to function as a trigger kinase that phosphorylates and activates Cdc25C prior to the activation of cyclin B-Cdc2 and thereby initiates its activation. However, the upstream regulation of Plk1 activation remains unclear. Here we have studied the interplay between Plk1 and Cdc2 through meiotic and early embryonic cycles in starfish. Distinct kinases, cyclin B-Cdc2, MAPK along with cyclin B- and/or cyclin A-Cdc2 and cyclin A-Cdc2, were unique upstream regulators for Plk1 activation at meiosis I, meiosis II and embryonic M-phase, respectively, indicating that Plk1 is not the trigger kinase at meiotic reinitiation. When Plk1 was required for cyclin B-Cdc2 activation, the action of Plk1 was mediated primarily through suppression of Myt1 rather than through activation of Cdc25. We propose that Plk1 can be activated by either cyclin A- or cyclin B-Cdc2, and its primary target is Myt1.

Animals↗

PubMed2003

A cyclooxygenase-2 inhibitor attenuates spontaneous and TNF-alpha-induced non-rapid eye movement sleep in rabbits.

Sleep is regulated in part by the brain cytokine network, including tumor necrosis factor-alpha (TNF-alpha). TNF-alpha activates the transcription factor nuclear factor-kappaB, which in turn promotes transcription of many genes, including cyclooxygenase-2 (COX-2). COX-2 is in the brain and is an enzyme responsible for production of prostaglandin D2. The hypothesis that central COX-2 plays a role in the regulation of spontaneous and TNF-alpha-induced sleep was investigated. Three doses (0.5, 5, and 50 microg) of NS-398, a highly selective COX-2 inhibitor, were injected intracerebroventricularly. The highest dose decreased non-rapid eye movement sleep. The intermediate and highest doses decreased electroencephalographic slow-wave activity; the greatest reduction occurred after 50 microg of NS-398 during the first 3-h postinjection period. Rapid eye movement sleep and brain temperature were not altered by any dose of NS-398. Pretreatment of rabbits with 5 or 50 microg of NS-398 blocked the TNF-alpha-induced increases in non-rapid eye movement sleep, electroencephalographic slow-wave activity, and brain temperature. These data suggest that COX-2 is involved in the regulation of spontaneous and TNF-alpha-induced sleep.

Animals↗

PubMed2003

Association of a polymorphism of the phospholipase D2 gene with the prevalence of colorectal cancer.

Phospholipase D plays an important role in transmembrane signaling in a variety of cell types and its activity is increased in certain cancers, suggesting that it also contributes to tumorigenesis. A C-->T transition at nucleotide 1814 of the human phospholipase D(2) gene, which results in a Thr-->Ile substitution at amino acid 577, was noted in the GenBank database. The relationship of this polymorphism to the prevalence of cancer of the esophagus, stomach, colon-rectum, lung, and breast in Japanese was investigated in a case-control study. The genotype of the phospholipase D(2) gene was determined by the polymerase chain reaction with confronting two-pair primers. Multivariate logistic regression analysis with adjustment for age, gender, and smoking status revealed that the frequency of the T allele of the 1814C-->T polymorphism was significantly higher in individuals with colorectal cancer than in controls. A significant association of the polymorphism with the prevalence of colorectal cancer was found in analyses assuming either dominant (TT+CT vs. CC) or additive (CT vs. CC) effects of the T allele, but the T allele was not associated with the prevalence of esophageal, gastric, lung, or breast cancer. The activities of phospholipase D in cell lysates or membrane fractions did not differ between cells transfected with cDNAs encoding the Thr-577 or Ile-577 variants of phospholipase D(2). These results suggest that the phospholipase D(2) gene is a susceptibility locus for colorectal cancer in Japanese individuals, although a functional effect of the 1814C-->T (Thr577Ile) polymorphism was not detected.

Colorectal Neoplasms↗

PubMed2003

Localized relapse in bone marrow in a posttransplantation patient with t(6;9) acute myeloid leukemia.

We report a 38-year-old woman with t(6;9) acute myeloid leukemia who relapsed with localized leukemic cell growth in the bone marrow after she had undergone allogeneic bone marrow transplantation. The localized cell growth was first recognized by an apparent discrepancy in the DEK-CAN fusion transcript levels between the aspirates from the left and right iliac bone marrow. Magnetic resonance imaging of the iliac bone revealed localized cell accumulation in the left side. The nonhomogeneous and localized leukemic cell growth in this case may have been due to the graft-versus-leukemia effect following allogeneic transplantation with donor lymphocyte infusion. Serial monitoring of molecular markers for leukemia at different sites or magnetic resonance imaging of the bone marrow may be of value in detecting this type of relapse.

Adult↗

PubMed2003

Pancreatic regeneration after ethionine-induced acute pancreatitis in rats lacking pancreatic CCK-A receptor gene expression.

BACKGROUND: We examined the effects of cholecystokinin (CCK) on the development of ethionine-induced pancreatitis and pancreatic recovery. We used Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model lacking pancreatic CCK-A receptor gene expression. METHODS: Ethionine-induced pancreatitis was induced in the 7-week-old male OLETF rats and in a control group that does not lack the pancreatic CCK-A receptor, Long-Evans Tokushima Otsuka (LETO) rats. The two groups were maintained on a low-protein diet for 11 days. During the last 4 days of the low-protein diet, dl-ethionine 20 mg/100 g body weight was administered intraperitoneally once daily. Histologic and biochemical examinations of the pancreas were performed, and plasma CCK concentrations were measured on days 1, 4, and 7 after the last ethionine administration. RESULTS: Pancreatic histologic scores for inflammation, hemorrhage, and necrosis in the LETO and OLETF rats were highest on days 1 and 4, respectively. Pancreatic weight, DNA content, and protein level per DNA content in both groups decreased during the low-protein diet, and recovery signs were delayed in the OLETF rats. The highest plasma CCK concentrations in the LETO and OLETF rats were reached on days 1 and 4, respectively. CONCLUSIONS: Ethionine-induced pancreatitis developed in the OLETF rats, and their pancreatic regeneration was delayed in comparison to that in the LETO rats. Our results suggested that CCK plays an important role in the development of pancreatitis as well as in the pancreatic repair process.

Animals↗

PubMed2003

Effect of IS-741 on ethionine-induced acute pancreatitis in rats: relation to pancreatic acinar cell regeneration.

BACKGROUND: Tissue destruction arising from neutrophil infiltration of the pancreas and other organs in acute pancreatitis is supposed to be suppressed by IS-741. We studied the effect of IS-741 on acute pancreatitis induced by DL-ethionine in rats. METHODS: Rats fed with a low protein diet for 11 days received daily intraperitoneal administration of DL-ethionine (20 mg/100 g) for the last 4 days of the diet. To evaluate the therapeutic effect on ethionine-induced pancreatitis, IS-741 (10 mg/kg s.c.) was administered every 8 h beginning after the second ethionine injection (IS group). An equal volume of saline was used for control rats as alternative to IS-741 (control group). The rats were killed 1, 3, 5, and 7 days after the last injection of ethionine. Blood was collected to measure concentrations of the inflammatory cytokine, interleukin-8. Histologic and biochemical examinations of the pancreas were performed. The pancreatic weight, DNA content, and protein levels were determined. The pancreas was histologically examined. RESULTS: Pancreatic tissue in the control group showed marked infiltration of inflammatory cells, and acinar cell necrosis was widespread 1 day after the last injection of ethionine (day 1). The severity of acute pancreatitis was alleviated in rats treated with IS-741 (IS group). Pancreatic wet weight and DNA content in the IS group were higher than those in the control group on day 1. Pancreatic protein level per DNA in the IS group was higher than that in the control group on day 7. The plasma interleukin-8 level in the control group was higher than that in the IS group on day 5. CONCLUSIONS: Therapeutic administration of IS-741 ameliorated ethionine-induced acute pancreatitis in rats, and IS-741 could be a useful drug to treat patients with severe acute pancreatitis.

Animals↗

PubMed2003

A tumour-associated DEAD-box protein, rck/p54 exhibits RNA unwinding activity toward c-myc RNAs in vitro.

BACKGROUND: The rck/p54 protein of 473 amino acids belongs to the family of DEAD-box/putative RNA helicase proteins. DEAD-box proteins have been implicated in a wide variety of cellular processes ranging from the initiation of protein synthesis and ribosome biosynthesis to premRNA splicing by means of modifying the RNA structure. Our previous data suggested that rck/p54 positively affected the translation initiation of c-myc mRNA. RESULTS: The data obtained from morphological studies and surface plasmon resonance assays clearly indicated that the protein specifically bound to c-myc RNA transcripts (RNAs) and exhibited RNA unwinding activity toward c-myc RNAs in the presence of ATP in vitro. Experiments using a deletion mutant of rck/p54 retaining only its N-terminal 289 amino acids demonstrated that the deleted C-terminal 184 amino acid domain is involved in the RNA unwinding activity. CONCLUSION: These findings strongly suggest that rck/p54 may play an important role in translation initiation by restructuring mRNAs even in the cell and contribute to carcinogenesis.

DEAD-box RNA Helicases↗

PubMed2003

Antiviral activity of limitin against encephalomyocarditis virus, herpes simplex virus, and mouse hepatitis virus: diverse requirements by limitin and alpha interferon for interferon regulatory factor 1.

Limitin has sequence homology with alpha interferon (IFN-alpha) and IFN-beta and utilizes the IFN-alpha/beta receptor. However, it has no influence on the proliferation of normal myeloid and erythroid progenitors. In this study, we show that limitin has antiviral activity in vitro as well as in vivo. Limitin inhibited not only cytopathic effects in encephalomyocarditis virus- or herpes simplex virus (HSV) type 1-infected L929 cells, but also plaque formation in mouse hepatitis virus (MHV) type 2-infected DBT cells. In addition, administration of limitin to mice suppressed MHV-induced hepatitis and HSV-induced death. The antiviral activity may be mediated in part by 2',5'-oligoadenylate synthetase, RNA-dependent protein kinase, and Mx protein, which inhibit viral replication or degrade viral components, because limitin induced their mRNA expression and enzyme activity. While limitin has antiviral activity as strong as that of IFN-alpha in vitro (the concentration that provided 50% inhibition of cytopathic effect is approximately 30 pg/ml), IFN regulatory factor 1 (IRF-1) dependencies for induction of an antiviral state were different for limitin and IFN-alpha. In IRF-1-deficient fibroblasts, a higher concentration of limitin than of IFN-alpha was required for the induction of antiviral activity and the transcription of proteins from IFN-stimulated response element. The unique signals and the fewer properties of myelosuppression suggest that a human homolog of limitin may be used as a new antiviral drug.

Animals↗

PubMed2003

[Postoperative delirium after general anesthesia vs. spinal anesthesia in geriatric patients].

BACKGROUND: Influence of the type of anesthesia on postoperative delirium was examined in geriatric patients with femoral neck fracture. METHODS: Forty patients aged 70 or more were randomly allocated to receive either general anesthesia (sevoflurane, nitrous oxide in oxygen, G group, n = 21) or spinal anesthesia (0.5% bupivacaine, S group, n = 19). G group received the oxygen therapy during the 12-hour postoperative period. Postoperative assessments included the rate of postoperative delirium during the 4-day postoperative period, oxygen saturation during the 18-hour postoperative period, the value of hemoglobin at 1 postoperative day and the number of analgesics requirements during the 4-day postoperative period. RESULTS: The rate of postoperative delirium was similar between the two groups during the 4-day postoperative period. However, that of S group tended to be higher during the 1-day postoperative period. Postoperative analgesic effect and the value of hemoglobin at 1 postoperative day were similar between the two groups. Oxygen saturation was similar between the two groups except 6 hours after the operation. CONCLUSIONS: The type of anesthesia, general or spinal, does not affect the postoperative delirium in geriatric patients with femoral neck fracture.

Aged↗

PubMed2002

Interaction between Src homology 2 domain bearing protein tyrosine phosphatase substrate-1 and CD47 mediates the adhesion of human B lymphocytes to nonactivated endothelial cells.

CD47 modulates a variety of cell functions such as adhesion, spreading, and migration. Using a fusion protein consisting of the extracellular region of Src homology 2 domain bearing protein tyrosine phosphatase substrate-1 (SHPS-1) and the Fc portion of human Ig (SHPS-1-Ig) we investigated the effects of SHPS-1 as a ligand for CD47 on B lymphocytes. Although SHPS-1-Ig binding to human B cell lines was solely mediated via CD47, their binding capacity for soluble and immobilized SHPS-1-Ig varied among cell lines irrespective of the similar expression levels of CD47, suggesting that distinctive affinity/avidity states exist during B cell maturation. Nalm6 cell line and tonsilar B lymphocytes adhered to immobilized SHPS-1-Ig and showed polarization-like morphology. These effects of SHPS-1-Ig were blocked by anti-CD47 mAbs (B6H12 and SE5A5). Wortmannin, a phosphatidylinositol-3 kinase inhibitor, but not pertussis toxin significantly inhibited the polarization induced by the immobilized SHPS-1-Ig. Thus, SHPS-1 acts as an adhesive substrate via CD47 in human B lymphocyte. Immunohistochemical analyses indicated that SHPS-1 is expressed on high endothelial venule as well as macrophages in human tonsils. HUVECs also express SHPS-1 in the absence of any stimuli, and the adhesion of tonsilar B lymphocytes to nonactivated HUVECs was significantly inhibited by SE5A5, indicating that SHPS-1/CD47 interaction is involved in the adhesion. Our findings suggest that SHPS-1/CD47 interaction may contribute to the recruitment of B lymphocytes via endothelial cells under steady state conditions.

Antibodies, Monoclonal↗

PubMed2002

Human herpesvirus 6 meningoencephalitis successfully treated with ganciclovir in a patient who underwent allogeneic bone marrow transplantation from an HLA-identical sibling.

Human herpesvirus 6 (HHV-6) has recently been recognized as an important pathogen in immunocompromised hosts, such as patients who have undergone allogeneic bone marrow transplantation (allo-BMT). Here we report a case of HHV-6 meningoencephalitis in a patient who underwent allo-BMT from an HLA-identical sibling. The patient suffered from headache, high fever, tremor, and disorientation on day 35 after allo-BMT. Findings at magnetic resonance imaging, electroencephalography, and routine cerebrospinal fluid (CSF) examination suggested the presence of viral meningoencephalitis. We diagnosed HHV-6 meningoencephalitis by means of polymerase chain reaction (PCR) analysis of a CSF specimen. Successful treatment was achieved with ganciclovir. Because HHV-6 encephalitis has a potentially fatal and fulminant course, it is necessary that HHV-6 encephalitis be recognized as one of the central nervous system complications that can follow allo-BMT. PCR analysis for HHV-6 in the CSF specimen is necessary for appropriate diagnosis and treatment.

Adult↗

PubMed2002

Significance of measurement of high-sensitivity C-reactive protein in acute pancreatitis.

BACKGROUND: Determination of the severity of acute pancreatitis is difficult in the early phase after onset, and we often encounter difficulties in making decisions to initiate intensive care during the early phase. Therefore, there is real need for a simple and inexpensive method that can precisely evaluate the severity of acute pancreatitis. METHODS: In the present study, we measured serum C-reactive protein (CRP) levels in 20 patients with acute pancreatitis, using a high-sensitivity CRP (hs-CRP) assay method. RESULTS: CRP levels were as low as 1.0, 0.4, and 0.3 mg/dl in cases 2, 3, and 9, respectively, with severe acute pancreatitis. These three patients were hospitalized within 24 h after the onset of pancreatitis. Cases 2, 3, and 9 showed high hs-CRP levels, of 209 000, 68 600, and 154 000 ng/ml, respectively, and their interleukin (IL)-6 levels were above 500 pg/ml. The mean hs-CRP level was 222 760 +/- 32 197 ng/ml in patients with severe acute pancreatitis and 22 798 +/- 8216 ng/ml in patients with mild to moderate pancreatitis, with a significantly higher level in the severe cases. Cases 14, 16, and 20, with mild to moderate pancreatitis, had hs-CRP levels of 83 400, 1800, and 55 400 ng/ml, respectively. CONCLUSIONS: Measurement of hs-CRP levels is a simple and inexpensive method. The hs-CRP levels were found to significantly increase in the early phase of severe acute pancreatitis, suggesting that hs-CRP could possibly serve as an early indicator of the progression of acute pancreatitis into a serious state.

APACHE↗

PubMed2002

Akt inhibits Myt1 in the signalling pathway that leads to meiotic G2/M-phase transition.

In eukaryotes, entry into M-phase of the cell cycle is induced by activation of cyclin B-Cdc2 kinase. At G2-phase, the activity of its inactivator, a member of the Wee1 family of protein kinases, exceeds that of its activator, Cdc25C phosphatase. However, at M-phase entry the situation is reversed, such that the activity of Cdc25C exceeds that of the Wee1 family. The mechanism of this reversal is unclear. Here we show that in oocytes from the starfish Asterina pectinifera, the kinase Akt (or protein kinase B (PKB)) phosphorylates and downregulates Myt1, a member of the Wee1 family. This switches the balance of regulator activities and causes the initial activation of cyclin B-Cdc2 at the meiotic G2/M-phase transition. These findings identify Myt1 as a new target of Akt, and demonstrate that Akt functions as an M-phase initiator.

Amino Acid Sequence↗