Biomedical subjects

T Kishimoto

Publications and source records attributed to T Kishimoto.

At least 307 records · Page 17Linked to original sources

PubMed1998

[A case of renal pelvic cancer with high serum level of CA 19-9].

A case of left renal pelvic cancer with a high level of serum CA19-9 is reported. Radiological examination showed a left renal pelvic cancer with lymph node metastasis, but did not reveal any tumors producing CA19-9 in any other organs. Chemotherapy was performed in addition to left total nephroureterectomy. The serum level of CA19-9 decreased to the normal range within three weeks after the operation. Immunohistochemical examination demonstrated that CA19-9 might have been produced from the tumor cells themselves in this case.

Biomarkers, Tumor↗

PubMed1998

[A case of synchronous triple primary cancers of prostate, kidney and bladder].

A case of synchronous triple primary cancer occurring in the prostate, kidney and urinary bladder is reported. A 74-year-old man had been complaining of macroscopic hematuria, dysuria and residual sensation of urine since January 1994. Pathological analysis of prostate revealed poorly differentiated adenocarcinoma in March, 1994. Bone and Ga scintigraphy gave no evidence of metastasis. Computerized tomography (CT) revealed irregularity of a part of the margin of prostate (T2N0M0) and enhanced mass with a diameter of 3 cm localized at the hilus of the right kidney. Excretory urography showed a shadow defect in the right pelvis and elevation of the bladder base. In spite of the appearance of class 5 in urine cytology, no tumor was detected in the bladder by cystoscopy. Angiography confirmed the presence of a hypervascular tumor in the right kidney. He underwent right-sided nephroureterectomy in April, 1994, because not only right pelvic tumor but also right renal tumor was suspected. Histological examination of the renal tumor revealed clear cell carcinoma (T2N0M0). Then, he did not visit our hospital for 8 months. In January, 1995 a papillary broadbase tumor was found near the bladder neck by cystoscopy. Transurethral resection of the tumor (TUR-Bt) was performed in February, 1995. Pathological analysis of the tumor revealed TCC G1 pT1 (T1N0M0).

Adenocarcinoma↗

PubMed1998

[Bone and joint tuberculosis in the field of orthopedics].

In Japan the number of patients with bone and joint tuberculosis has been dramatically decreasing since the beginning of 1980's. The number of patients was 1626 in 1978 according to statistics of tuberculosis patient in Japan. This was only 2.02% of new tuberculosis patients of Japan in 1978. Since that time the number of patients with bone and joint tuberculosis, in Japan, has been in steady decline. The number was only 675 patients in 1996. This was only 1.34% of new tuberculosis patients. The rate of new infections also decreased. Recently due to the development of computed tomography, magnetic resonance imaging and so on, patients with bone and joint tuberculosis can be diagnosed early, with great certainty. Curettage of infected focus and bone grafting via anterior approach has resulted in consistently improved results. While there are many reports of about the operative treatment with spinal instruments for spinal tuberculosis, artificial materials must be implanted with great care.

Humans↗

PubMed1998

[Leiomyoma of the bladder: report of two cases].

We report 2 cases of leiomyoma of the urinary bladder. A 41-year-old female visited our hospital with the complaint of pollakisuria. A solid tumor of the urinary bladder was found by ultrasonography. A large shadow defect at the left-anterior wall was shown by drip infusion pyelography (DIP). Computed tomographic scan (CT) and magnetic resonance imaging (MRI) also revealed a large tumor. T1-weighted image revealed a homogeneous low intensity tumor and T2-weighted image disclosed heterogeneous low intensity tumor. Cystoscopy revealed a large submucosal tumor. Partial cystectomy was performed, and she has had neither recurrence nor metastasis for 36 months. A 32-year-old male was referred to our hospital with the complaint of macrohematuria. A solid tumor of the urinary bladder was found by ultrasonography. A shadow defect was not clearly detected by DIP. A large tumor was detected on the anterior wall by MRI. T1-weighted image showed a homogeneous low intensity tumor and T2-weighted image disclosed a high intensity tumor. Cystoscopy revealed a submucosal tumor on the anterior wall. Urine cytology did not suggest a malignancy. The biopsied specimens revealed only an inflammatory change in the mucosa. Partial cystectomy was carried out. He has had neither recurrence nor metastasis for 29 months. Histological diagnosis in both cases was leiomyoma of the urinary bladder.

Adult↗

PubMed1998

An indirect role for cyclin B-Cdc2 in inducing chromosome condensation in Xenopus egg extracts.

We have studied the cytoplasmic mechanism that induces metaphase chromosome condensation in cell-free Xenopus egg extracts. To analyze the mechanism responsible for inducing chromosome condensation separately from those responsible for sperm chromatin remodeling and nuclear envelope disassembly, we used Xenopus sperm chromatin that had already been remodeled to nucleosomal chromatin by incubating demembranated sperm with egg extracts added with lysolecithin. We found that inhibition of cyclin B-Cdc2 with butyrolactone I abolished chromosome condensation of the remodeled sperm chromatin by M-phase egg extracts, but incubation of the chromatin with active cyclin B-Cdc2 alone did not induce chromosome condensation, indicating a requirement for cytoplasmic factor(s) in addition to cyclin B-Cdc2 for the induction of chromosome condensation. We further demonstrated that if the cyclin B-Cdc2-dependent phosphorylation state was protected against dephosphorylation by a preincubation of M-phase extracts with ATP-gamma-S, chromosome condensation and phosphorylation of chromosomal histone H1 occurred even when extracts were depleted of cyclin B-Cdc2 activity. The chromosome condensation seen in the absence of cyclin B-Cdc2 was completely inhibited with another protein kinase inhibitor, 6-dimethylaminopurine, implying that a protein kinase other than cyclin B-Cdc2 was involved in the induction of chromosome condensation. These results strongly suggest that a cyclin B-Cdc2-dependent protein kinase cascade is involved in inducing chromosome condensation and the phosphorylation of chromosomal histone H1.

Animals↗

PubMed1997

MAP4 is the in vivo substrate for CDC2 kinase in HeLa cells: identification of an M-phase specific and a cell cycle-independent phosphorylation site in MAP4.

We reported previously that cdc2 kinase decreased the microtubule-stabilizing ability of a major HeLa cell microtubule-associated protein, MAP4, by phosphorylation in vitro [Ookata, K., et al. (1995) J. Cell Biol. 128, 849-862]. An important question raised by this study is whether MAP4 is indeed phosphorylated by cdc2 kinase at mitosis in vivo. We present here evidence that cdc2 kinase is the major M-phase MAP4 kinase, and, further, we identify two phosphorylation sites within the proline-rich domain of MAP4. Metabolic 32P labeling showed the increased phosphorylation of MAP4 at mitosis. A specific inhibitor of cdc2 kinase, butyrolactone I, inhibited phosphorylation of MAP4 both in mitotic HeLa cells and in the mitotic HeLa cell extract. The phosphopeptide map analysis revealed the high similarity of in vivo labeled mitotic MAP4 to that phosphorylated by cdc2 kinase in vitro. Ser-696 and Ser-787, both of which lie within SPXK consensus sequences for cdc2 kinase, were identified as phosphorylation sites in the proline-rich region of MAP4 in vivo and in vitro. Immunoblotting with antibodies that recognize the phosphorylation state of Ser-696 or Ser-787 showed that Ser-787 in the SPSK sequence was specifically phosphorylated at mitosis while Ser-696 in the SPEK sequence was phosphorylated both at mitosis and in interphase. These results suggest that cdc2 kinase directly regulates microtubule dynamics at mitosis through phosphorylation of MAP4 at a number of sites, including Ser-787.

4-Butyrolactone↗

PubMed1997

Defective adipocyte differentiation in mice lacking the C/EBPbeta and/or C/EBPdelta gene.

To investigate the role of C/EBP family members during adipocyte differentiation in vivo, we have generated mice lacking the C/EBPbeta and/or C/EBPdelta by gene targeting. Approximately 85% of C/EBPbeta(-/-).delta(-/-) mice died at the early neonatal stage. By 20 h after birth, brown adipose tissue of the interscapular region in wild-type mice contained many lipid droplets, whereas C/EBPbeta(-/-).delta(-/-) mice did not accumulate droplets. In addition, the epidydimal fat pad weight of surviving adult C/EBPbeta(-/-).delta(-/-) mice was significantly reduced compared with wild-type mice. However, these adipose tissues in C/EBPbeta(-/-).delta(-/-) mice exhibit normal expression of C/EBPalpha and PPARgamma, despite impaired adipogenesis. These results demonstrated that C/EBPbeta and C/EBPdelta have a synergistic role in terminal adipocyte differentiation in vivo. The induction of C/EBPalpha and PPARgamma does not always require C/EBPbeta and C/EBPdelta, but co-expression of C/EBPalpha and PPARgamma is not sufficient for complete adipocyte differentiation in the absence of C/EBPbeta and C/EBPdelta.

Adipocytes↗

PubMed1997

Simultaneous activation of signals through gp130, c-kit, and interleukin-3 receptor promotes a trilineage blood cell production in the absence of terminally acting lineage-specific factors.

We assessed the biologic role of signaling through gp130, a signal-transducing receptor (R) component, in human hematopoiesis in vitro. Although peripheral blood-derived CD34(+) cells ubiquitously expressed gp130 and interleukin-3 receptor alpha (IL-3Ralpha), IL-6Ralpha was only detected on 80% of these CD34(+) cells. We sorted CD34(+)IL-6R+ or CD34(+)IL-6R- cells and studied the effect on hematopoietic colony formation of signaling through gp130 activated by IL-6 or a combination of IL-6 and recombinant soluble human IL-6R (sIL-6R) in the presence or absence of stem cell factor (SCF ) and/or IL-3. Signals activated by SCF, IL-6, or IL-6/sIL-6R complex alone did not induce significant colony formation. However, a combination of IL-3, SCF, and IL-6/sIL-6R complex dramatically induced many neutrophil (colony-forming unit-granulocyte [CFU-G]), erythroid burst (burst-forming unit-erythrocyte [BFU-E]), erythrocyte-containing mixed (CFU-Mix), and megakaryocyte (CFU-Meg) colony formations when CD34(+)IL-6R- cells were used as the target. CFU-G colony formation induced by the three signals was more evident when CD34(+)IL-6R+ cells were used as the target. This distinct synergistic effect of the three different signals was confirmed by single-cell clone-sorting experiments. Moreover, colony formation (including CFU-G, BFU-E, CFU-Mix, and CFU-Meg) was observed even in the presence of neutralizing antibodies for granulocyte colony-stimulating factor, erythropoietin, and thrombopoietin (c-Mpl), whereas neutralizing antibodies for gp130, IL-6R, IL-3, and SCF partially or completely blocked the synergistic effect. The maturation of neutrophilic, erythroid, and megakaryocytic cells supported by the three signals in serum-free cultures was confirmed by immunostaining using anti-CD66b, antiglycophorin A, antihemoglobin alpha, and anti-CD41 monoclonal antibodies, respectively. In contrast, any two of the three signals were insufficient for effective blood cell production in the absence of maturation factors. These results suggest that simultaneous activation of the three signals through gp130, c-kit, and IL-3R can induce in vitro proliferation and differentiation of trilineage hematopoietic progenitors in the absence of terminally acting lineage-specific factors.

Animals↗

PubMed1997

Universal skew of T cell receptor (TCR) V beta usage for Crohn's disease (CrD).

It would be of clear interest and importance to identify T cell populations which correlate with the initiation of some T cell-mediated diseases; however, it is difficult to observe the initial response of T cells in these diseases because of modification due to immunosuppressive treatment. We investigated T cell receptor (TCR) V beta usage in both affected and unaffected mucosa from 16 patients with active Crohn's disease (CrD), undergoing nutritional therapy without any immunomodulatory medications. Semiquantitative reverse transcriptase-polymerase chain reaction showed increased expression of V beta 12 and 13 in the entire mucosa of CrD but not in the controls. This was confirmed by introducing a random cloning method. Such skewing was observed primarily in CD4+ lamina propria lymphocytes. DNA sequence analysis demonstrated a striking clonal expansion of V beta 12 T cells, but the dominant clones were not identical in the patients. These findings suggest the importance of superantigen as well as specific T cell response in the pathogenesis of CrD.

Adult↗

PubMed1997

Cyclin D1 overexpression in rat two-stage bladder carcinogenesis and its relationship with oncogenes, tumor suppressor genes, and cell proliferation.

Overexpression of cyclin D1 has been implicated in the malignant transformation of a variety of human cancers, including urinary bladder carcinomas. However, few reports have addressed the significance of cyclin D1 overexpression in chemical carcinogenesis in rodents. In the present study, we evaluated the oncogenic potential of cyclin D1 in experimental rat urinary bladder carcinogenesis and its relationships to the oncogenes cyclin E, K-ras, and H-ras as well as tumor suppressor genes p53 and p21WAF1/Cip1. In addition, proliferation status of preneoplastic lesions and tumors was assessed by proliferating cell nuclear antigen immunohistochemistry. Fisher 344 rats were initiated with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine in the drinking water for 4 weeks and then administered 5% sodium L-ascorbate in diet. Animals were sacrificed at weeks 4, 8, 12, 18, and 24. Preneoplastic lesions such as papillary or nodular hyperplasia and neoplastic lesions of the urinary bladder were observed during carcinogenesis. By immunohistochemical examination, overexpression of cyclin D1 protein was observed in 17% of papillary or nodular hyperplasias, 66% of papillomas, and 69% of transitional cell carcinomas, whereas nuclear accumulation of p53 was observed in none of the preneoplastic lesions and in fewer than 2% of transitional cell carcinomas. Overexpression of cyclin D1 in preneoplastic lesions and tumors was not dependent on the size of the tumors or their proliferation status. Quantitation of mRNA in tumors by multiplex reverse transcription-PCR showed that average mRNA expression of cyclin D1 and cyclin E was increased, whereas average p21WAF1/Cip1 mRNA expression was decreased. More than 2-fold overexpression of cyclin D1 mRNA was observed in 50 and 60% of tumors at weeks 18 and 24, respectively. Localization of cyclin D1 mRNA expression was demonstrated by in situ hybridization, and the results were comparable to immunohistochemistry findings. None of the 25 tumors we examined by PCR-single-strand conformational polymorphism analysis harbored p53 mutations, H-ras mutations, or K-ras mutations. Thus, during the promotion phase of two-stage bladder carcinogenesis, overexpression of cyclin D1 in tumor cells may provide yet another mechanism by which tumors can gain a growth advantage. In contrast, tumors with mutated p53 may not have a growth advantage. Our results suggest that overexpression of cyclin D1 plays a critical role during urinary bladder carcinogenesis.

Animals↗

PubMed1997

A small molecule CXCR4 inhibitor that blocks T cell line-tropic HIV-1 infection.

Several members of the chemokine receptor family have been shown to function in association with CD4 to permit human immunodeficiency virus type 1 (HIV-1) entry and infection. The CXC chemokine receptor CXCR4/fusin is a receptor for pre-B cell growth stimulating factor (PBSF)/stromal cell-derived factor 1 (SDF-1) and serves as a coreceptor for the entry of T cell line-tropic HIV-1 strains. Thus, the development of CXCR4 antagonists or agonists may be useful in the treatment of HIV-1 infection. T22 ([Tyr5,12,Lys7]-polyphemusin II) is a synthesized peptide that consists of 18 amino acid residues and an analogue of polyphemusin II isolated from the hemocyte debris of American horseshoe crabs (Limulus polyphemus). T22 was found to specifically inhibit the ability of T cell line-tropic HIV-1 to induce cell fusion and infect the cell lines transfected with CXCR4 and CD4 or peripheral blood mononuclear cells. In addition, T22 inhibited Ca2+ mobilization induced by pre-B cell growth stimulating factor (PBSF)/SDF-1 stimulation through CXCR4. Thus, T22 is a small molecule CXCR4 inhibitor that blocks T cell line-tropic HIV-1 entry into target cells.

3T3 Cells↗

PubMed1997

Phosphorylation states of microtubule-associated protein 2 (MAP2) determine the regulatory role of MAP2 in microtubule dynamics.

Phosphorylation-dependent regulation of microtubule-stabilizing activities of microtubule-associated protein 2 (MAP2) was examined using optical microscopy. MAP2, purified from mammalian brain, was phosphorylated by either cAMP-dependent protein kinase (PKA) or cyclin B-dependent cdc2 kinase. Using PKA, 15 mol of phosphoryl groups was incorporated per mole of MAP2, but about 70% of the phosphates was distributed to the projection region. Using cdc2 kinase, 7-10 mol of phosphoryl groups was incorporated per mole of MAP2, and more than 60% of the phosphates was distributed to the microtubule-binding region. Both types of phosphorylation similarly reduced binding activity of MAP2 onto microtubules. Direct observation of individual microtubules using dark-field microscopy showed that interconversion between the polymerization phase and the depolymerization phase was repeated in both unphosphorylated and PKA-phosphorylated MAP2. In cdc2 kinase-phosphorylated MAP2, however, the phase transition from depolymerization to polymerization occurred with difficulty, with the result being that the half-life of individual microtubules was as short as in the absence of MAP2. Examination of spontaneous polymerization of microtubules using dark-field microscopy showed that the microtubule-nucleating activity of MAP2 was reduced by PKA-dependent phosphorylation and was completely abolished by cdc2 kinase-dependent phosphorylation. These observations show that cdc2 kinase-dependent phosphorylation inhibits both the microtubule-stabilizing activity and the microtubule-nucleating activity of MAP2, while PKA-dependent phosphorylation affects only the microtubule-nucleating activity of MAP2.

Animals↗

PubMed1997

Phosphorylation of retinoblastoma protein at apoptotic cell death in rat neuroblastoma B50 cells.

Phosphorylation of the retinoblastoma protein (RB) was observed during apoptosis of B50 neuroblastoma cells following induction by dibutyryl cAMP, after differentiation into neurons, or by cycloheximide during proliferation. A weak but distinct increase in a RB and histone H1 kinase activity was detected at the time of RB phosphorylation. However, the RB kinase appeared to correspond to neither p34cdc2 kinase, CDK2 nor CDK5 because it was not inhibited by butyrolactone I, an inhibitor for them. Expression of CDK4 and 6 along with several cyclins also did not coincide with the appearance of phosphorylated RB in the apoptotic process.

4-Butyrolactone↗

PubMed1997

New xenograft model of multiple myeloma and efficacy of a humanized antibody against human interleukin-6 receptor.

A new xenograft model of multiple myeloma (MM), where growth is strongly regulated by interleukin-6 (IL-6), was established in severe combined immunodeficiency (SCID) mice. In this model, endogenous IL-6 from SCID mice was ineffective at eliciting growth of the established human MM cell line KPMM2; these cells achieved autonomous growth through their autocrine secretion of IL-6. The etiopathology in this disease model is consistent with that of human MM. When greater than 3 x 10(6) KPMM2 cells were injected intravenously (IV), tumors developed in all mice and were predominantly localized in their bone marrow. Tumors were also apparent in the lymph nodes, but absent from other organs. Immunostaining of cell surface antigen (CD38) showed that more than 40% of bone marrow cells in femur were of myeloma origin in the advanced stage of tumor progression (day 37). Histologic analysis of these mice show that bone marrow was largely occupied by plasmablastic cells and bones had developed osteolytic lesions at multiple sites. Concurrently, there was a decrease in bone density throughout the body and a significant increase in ionized plasma calcium. M-protein was detected in the serum within 10 days after transplantation, which correlated with the tumor progression. Between 30 and 40 days after the transplantation, mice presented with a rapid and severe loss of body weight, hind leg paralysis, and fatigue. Subsequently, the mice died within a week. A single IV injection of 0.2 mg humanized anti-IL-6 receptor antibody (hPM1) into mice on the day after tumor transplantation substantially suppressed the elevation of serum M-protein and development of the tumor-associated abnormalities and significantly increased in the life span of tumor-bearing mice. Our data show the usefulness of this model to analyze the pathologic role of IL-6 in MM and the efficacy of targeting the IL-6 receptor in IL-6-dependent KPMM2 cells.

Animals↗

PubMed1997

SUG1, a component of the 26 S proteasome, is an ATPase stimulated by specific RNAs.

SUG1 is an integral component of the 26 S proteasome. Belonging to a novel putative ATPase family, it shares four conserved motifs characteristic of ATP-dependent DNA/RNA helicases. Recombinant rat SUG1 (rSUG1) produced in Escherichia coli was highly purified and characterized in terms of its biochemical properties. The rSUG1 exhibited a Mg2+-dependent ATPase activity. The Km for ATP and Vmax of rSUG1 were 35 microM and 7 pmol of ATP/min/microg of protein, respectively. Both ATPase activity to release [32P]monophosphate and [32P]ATP-labeling activity were coordinately affected by cold ATP severely, GTP and UTP moderately, and CTP little. Interestingly, the rSUG1 ATPase activity was stimulated by poly(U) and poly(C), but not by poly(A), poly(G), or by any forms of DNAs tested. A UV cross-linking assay also indicated poly(U)- and poly(C)-stimulated labeling of rSUG1 with [alpha-32P]ATP. Moreover, the ATPase activity was facilitated by cellular poly(A)+ RNA, but not by poly(A)- RNA. RNA transcribed in vitro from cDNA encoding a b-Zip protein could stimulate the ATPase activity. This is the first report to demonstrate a specific RNA requirement for ATPase with respect to the proteasomal ATPases. Our present work suggests that SUG1 can specifically interact with protein-coding RNA (mRNA) and play some roles in mRNA metabolism.

Adenosine Triphosphatases↗

PubMed1997

Hepatoma-derived growth factor belongs to a gene family in mice showing significant homology in the amino terminus.

Hepatoma-derived growth factor (HDGF) is an acidic polypeptide with mitogenic activity for fibroblasts performed outside the cells despite the presence of a putative nuclear localization signal (NLS). We have now cloned three related mouse cDNAs: one for a mouse homologue of human HDGF and two for additional HDGF-related proteins provisionally designated HDGF-related proteins 1 and 2 (HRP-1 and -2). Their deduced sequences have revealed that HDGF belongs to a new gene family with a highly conserved 98-amino-acid sequence at the amino terminus (hath region, for homologous to the amino terminus of HDGF). HRP-1 and HRP-2 proteins are 46 and 432 amino acids longer than mouse HDGF, respectively, and have no conserved amino acid sequence other than the hath region. HRP-1 is a highly acidic protein (26% acidic) and also has a putative NLS. HRP-2 protein carries a mixed charge cluster, a sharp switch of positive-to negative-charge residues, which is often found in some nuclear proteins. Northern blotting shows that mouse HDGF and HRP-2 are expressed predominantly in testis and skeletal muscle, to intermediate extents in heart, brain, lung, liver, and kidney, and to a minimal extent in spleen. HRP-1 is expressed specifically in testis. These findings suggest that the HDGF gene family might play a new role in the nucleus especially in testis.

Amino Acid Sequence↗

PubMed1997

Cloning and functional analysis of new members of STAT induced STAT inhibitor (SSI) family: SSI-2 and SSI-3.

Upon the corresponding ligand's stimulation, the cytokine receptors activate several signal pathways: JAK-STAT pathway, Ras-MAP kinase pathway and so on. Recently, we demonstrated that one of the STAT3 (signal transducer and activator of transcription-3) target genes could suppress the function of STAT3 and designated as SSI-1(STAT induced STAT inhibitor-1). SSI-1 is thought to play a critical role in negative feedback control of JAK-STAT signaling pathway. In the present study, we identified two novel human genes which products have homologous region in their SH2 domain and its COOH-terminal region to mouse SSI-1. Northern blotting analysis and functional studies demonstrated that SSI-2 and SSI-3 mRNA were also induced by cytokine stimulation and their forced expression in mouse myeloid leukemia cell, M1, suppressed the apoptotic effect of LIF, like SSI-1. We also demonstrated the structure of human SSI-1.

Amino Acid Sequence↗

PubMed1997

MAP kinase links the fertilization signal transduction pathway to the G1/S-phase transition in starfish eggs.

The mechanism by which fertilization initiates S-phase in the zygote is examined by manipulating the activity of MAP kinase in mature starfish eggs. These unfertilized eggs, which are arrested at G1-phase after the completion of meiosis, have high MAP kinase activity but undetectable cdc2 kinase activity. Either fertilization or inhibition of protein synthesis causes a decrease in MAP kinase activity, which is followed by DNA synthesis. Inactivation of MAP kinase with its specific phosphatase, CL100, initiates DNA synthesis in the absence of fertilization, while constitutive activation of MAP kinase with MEK represses the initiation of DNA synthesis following fertilization. Thus, in unfertilized mature starfish eggs, a capacity for DNA replication is already acquired, but entry into S-phase is negatively regulated by MAP kinase activity that is supported by a continuously synthesized protein(s) but not by cdc2 kinase. Upon fertilization, downregulation of MAP kinase activity is necessary and sufficient for triggering the G1/S-phase transition.

Adenine↗