Activation of protein kinase C induces differentiation in the human T-lymphoblastic cell line MOLT-3

Yamauchi, Yusuke; Nagasawa, Kohei; Mayumi, Takehito; Horiuchi, Takahiko; Niho, Yoshiyuki

doi:10.1038/bjc.1989.211

Cited by 11 publications

(5 citation statements)

References 28 publications

(24 reference statements)

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“…TPA is a well known, potent inducer of di erentiation in cells such as myeloid leukemia cells and neuroblastoma (Rovera et al, 1979(Rovera et al, , 1982Bouche et al, 1995;Heikkila et al, 1989;Yamauchi et al, 1989). We previously showed that the androgen-independent human prostate cancer cell line TSU-Pr1 di erentiates into microglia-like cells upon treatment with TPA (Itayasu et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Upregulation of p21WAF1/CIP1 leads to morphologic changes and esterase activity in TPA-mediated differentiation of human prostate cancer cell line TSU-Pr1

et al. 2001

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We reported previously that human prostate cancer cell line TSU-Pr1 can di erentiate into microglia-like cells by 12-O-tetra-decanoylphorbol-13-acetate (TPA) treatment. In this study, we identi®ed a signal transduction pathway involved in TPA-induced TSU-Pr1 cell di erentiation and investigated the mechanism of growth arrest that accompanies this di erentiation. TPAinduced di erentiation and growth arrest of TSU-Pr1 cells were inhibited by treatment with Protein kinase C (PKC) inhibitor GF109203X and mitogen-activated protein (MAP) kinase inhibitor PD98059. Treatment of TSU-Pr1 cells with TPA for 15 min or longer resulted in translocation of PKCa, PKCg, and PKCe from cytosolic to membrane fraction. Our results suggest that TPAinduced TSU-Pr1 cell di erentiation is associated with activation of MAP kinase and PKCa, PKCg, and PKCe. The mechanism of growth arrest in TSU-Pr1 cells that underwent TPA-induced di erentiation were examined for factors in the signaling pathway downstream of MAP kinase that control the cell cycle. Upregulation of p21 WAF1/CIP1 cyclin-dependent kinase inhibitor protein was observed in a manner dependent on PKC or MAP kinase. Moreover, adenovirus-mediated overexpression of recombinant p21 WAF1/CIP1 in TSU-Pr1 cells result in growth arrest, morphological change to microglia-like cells, and increased a-naphthyl acetate esterase activity, all of which are associated with cellular di erentiation. Thus, our results indicate that p21 WAF1/CIP1 mediates TPA-induced growth arrest and di erentiation of TSUPr1 cells. Oncogene (2001) 20, 1220 ± 1228.

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Section: Discussionmentioning

confidence: 99%

Upregulation of p21WAF1/CIP1 leads to morphologic changes and esterase activity in TPA-mediated differentiation of human prostate cancer cell line TSU-Pr1

et al. 2001

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“…3T3 mouse fibroblasts (12) and resting T lymphocytes (13) and 2) inhibition of cell proliferation and stimulation of differentiation. The latter effect was first demonstrated when the HL60 promyelocytic leukemia cell line was induced to differentiate into a macrophage like phenotype (14) and subsequently the same phenomenon was observed in other cell types (15). Protein kinase C participates in a complex network of signal transduction pathways involving both tyrosine kinase receptors and G protein coupled receptors.…”

Section: Introductionmentioning

confidence: 82%

Protein kinase C modulates the up-regulation of the pyrimidine biosynthetic complex, CAD, by MAP kinase

et al. 2007

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The multifunctional protein CAD initiates de novo pyrimidine biosynthesis in mammalian cells. CAD is activated by MAP kinase (Erk1/2) just prior to the S phase of the cell cycle, when the demand for pyrimidine nucleotides is greatest, and down-regulated as the cells emerge from S phase by protein kinase A (PKA) phosphorylation. MAP kinase phosphorylates Thr456, while PKA phosphorylates Ser1406 and Ser1859, although only Ser1406 is involved in regulation. LC/mass spectrometry showed that Ser1873, a residue that lies within a putative protein kinase C (PKC) consensus sequence is also phosphorylated. Purified CAD was reacted with ATP and a panel of eight PKC isozymes. Most isozymes resulted in limited CAD phosphorylation, but the delta and epsilon isozymes were most effective. While the level of Thr456 phosphorylation is very low in confluent cells, exposure of stationary BHK 165-23 cells to the PKC activator, phorbol 12-myristate-13-acetate (PMA) resulted in a 3-fold increase in the modification of this residue. The stimulation of Thr456 phosphorylation was blocked by PKC inhibitors. The PKA inhibitor, H-89, also stimulated PMA-induced Thr456 modification probably because PKA mediated phosphorylation of CAD Ser1406 antagonizes the MAP kinase phosphorylation. Thus, the extent of Thr456 phosphorylation and the activation of pyrimidine biosynthesis depend on the synergistic and antagonistic interactions of three signaling pathways, MAP kinase, PKC and PKA. Deletions mutants lacking the putative PKC site, Ser1873 do not exhibit PMA induced Thr456 phosphorylation. We conclude that the activating MAP kinase phosphorylation of CAD proceeds through a PKC dependent pathway.

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“…stimulation of quiescent cells into growth and subsequent mitosis or inhibition of cell proliferation and stimulation of terminal differentiation. 16,17 It was worthy to mention that TPA could be found in many Chinese medicinal herbs and food-types which suggested that the diet of Chinese individual might make them more vulnerable to NPC. 4,5,18,19 So the original intention of our present study was to use proteomics technology to seek some key proteins which could help to clarify the mechanism of TPA promoting NPC.…”

Section: Discussionmentioning

confidence: 99%

“…Former studies showed that a number of cultured cell lines were responsive to TPA to fall into two categories, viz. stimulation of quiescent cells into growth and subsequent mitosis or inhibition of cell proliferation and stimulation of terminal differentiation. , …”

Section: Discussionmentioning

confidence: 99%

Proteome Analysis of Antiproliferative Mechanism of 12-O-Tetradecanoylphorbol 13-Acetate on Cultured Nasopharyngeal Carcinoma CNE2 Cells

Jiang¹,

Ming²,

Huang³

et al. 2005

J. Proteome Res.

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12-O-Tetradecanoyl-phorbol-13-acetate (TPA) is a plant derivative with multiple function as tumor promoter, differentiation revulsant or leukemia therapy drug. The molecular mechanism of its function is perplexing. Many studies have focused on the mechanism of TPA stimulation in tumor promotion of mouse models or terminal differentiation of leukemia cells, but the effect of TPA on nasopharyngeal carcinoma (NPC) remains unclear, while TPA was considered to be associated with NPC development. In the present study, we employed proteomics techniques to study protein changes of a poorly differentiated squamous carcinoma cell line-CNE2 of human NPCs cells induced by TPA. Six significantly and reproducibly changed proteins were identified and their functional implications were discussed in some details.

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Activation of protein kinase C induces differentiation in the human T-lymphoblastic cell line MOLT-3

Cited by 11 publications

References 28 publications

Upregulation of p21WAF1/CIP1 leads to morphologic changes and esterase activity in TPA-mediated differentiation of human prostate cancer cell line TSU-Pr1

Upregulation of p21WAF1/CIP1 leads to morphologic changes and esterase activity in TPA-mediated differentiation of human prostate cancer cell line TSU-Pr1

Protein kinase C modulates the up-regulation of the pyrimidine biosynthetic complex, CAD, by MAP kinase

Proteome Analysis of Antiproliferative Mechanism of 12-O-Tetradecanoylphorbol 13-Acetate on Cultured Nasopharyngeal Carcinoma CNE2 Cells

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