Signal perception and transduction: the role of protein kinases

Schenk, Paul W.; Snaar-Jagalska, B. E.

doi:10.1016/s0167-4889(98)00178-5

Cited by 190 publications

(105 citation statements)

References 167 publications

Supporting

Mentioning

105

Contrasting

Order By: Relevance

“…PKC has been considered to act upstream of the signal transduction pathway of MEK, ERK, and JNK [47][48][49]. PKC is also known to play an important role in the process of apoptosis [50][51][52] and in growth regulation [ 53 ].…”

Section: Activation By Ts Of Pkcmentioning

confidence: 99%

Tocopheryl Succinate—Versatile Functions due to Its Unique Physicochemical Properties

Kogure

Fukuzawa

2004

J. Clin. Biochem. Nutr.

View full text Add to dashboard Cite

Summary ␣ -Tocopheryl succinate (TS), a succinyl ester of ␣ -tocopherol ( ␣ -T), has no antioxidant activity, but it does have unique physicochemical properties and shows versatile biological functions. The physicochemical properties of TS affect the structure and function of lipid membranes, and the ability to form bilayer vesicles by itself suggests that TS can become a new carrier in the field of drug delivery systems. The ability to induce apoptosis is a most attractive property of TS. Because TS shows higher cytotoxicity on various cancer cells than on normal cells in vitro , prevents tumor growth, and extends survival in vivo , much attention has been paid to TS as a new type of anti-cancer drug. Activation of various signal transduction factors is also a well-known function of TS. In particular, protein kinase C (PKC), which acts in upstream in the signal transduction, is thought to play an important role in the effects of TS. Our theoretical computational study indicates that TS activates PKC by direct interaction with PKC due to its high structural flexibility.

show abstract

Section: Activation By Ts Of Pkcmentioning

confidence: 99%

Tocopheryl Succinate—Versatile Functions due to Its Unique Physicochemical Properties

Kogure

Fukuzawa

2004

J. Clin. Biochem. Nutr.

View full text Add to dashboard Cite

show abstract

“…The present observation that activation of PKC promotes human cancer cell growth through suppression of human p18 INK4c may support the possibility that p18 INK4c also plays some part in human tumorigenesis. Situated at the crossroads of many signal transduction pathways, PKCs are activated by upstream signaling elements such as growth factor receptors (for example, platelet-derived growth factor receptor), and are able to activate downstream signaling molecules such as the proto-oncogene Raf-1 (Schenk and Snaar-Jagalska, 1999;Liebmann, 2001). In fact, PKC activity is increased in some human tumors compared with their normal counterpart (O'Brian et al, 1989;Alvaro et al, 1992;Gordge et al, 1996).…”

mentioning

confidence: 99%

Activation of protein kinase C promotes human cancer cell growth through downregulation of p18INK4c

et al. 2004

View full text Add to dashboard Cite

p18 INK4c , a member of INK4 family of cyclin-dependent kinase inhibitors, negatively regulates the cyclin D-cyclindependent kinase 4/6 complexes which promote G1/S transition by phosphorylating the retinoblastoma tumorsuppressor gene product. Several recent studies using p18 INK4c -null mice revealed that the p18 INK4c plays an important role in cell proliferation and tumor development. We report here that 12-O-tetradecanoylphorbol-13-acetate (TPA), widely used as a protein kinase C (PKC) activator, suppresses the expression of p18 INK4c through its promoter, accompanied by the induction of human cancer cell growth. Reduction of p18 INK4c using small interfering RNA (siRNA) also enhanced cell growth, suggesting that p18 INK4c is a critical target of TPA. Ro 31-8425, a potent and highly specific PKC inhibitor abrogated the suppressive effect of TPA on p18 INK4c gene expression. However, the expression of dominant-negative c-Jun (TAM-67) did not inhibit the action of TPA on p18 INK4c . These findings suggest that activation of PKC promotes human cancer cell growth through downregulation of p18 INK4c in an AP-1 activation-independent manner. These results suggest that the accelerated cellular proliferation of some human tumors caused by enhanced PKC activity at least partially involves the suppression of p18 INK4c , which is a ubiquitously expressed cyclin-dependent kinase inhibitor.

show abstract

“…These mechanisms entail the alteration of gene expression at the transcriptional level (e.g., methylation of DNA or acetylation of DNAbinding proteins), translational level (e.g., alternative splicing or stability of mRNA), or posttranslational level (e.g., protein modification such as phosphorylation). Most tumor promoters are not mutagenic (e.g., phenobarbital, phorbol esters, polybrominated biphenyls, saccharin, peroxisome proliferators, TCDD, DDT) (14), but can alter differentiation (15), inhibit apoptosis (16,17), induce various signal transduction pathways (e.g., protein kinase C, mitogen activated protein kinases) (18), and activate gene expression (19). Similar to tumor-promoting chemicals, ELF-EMF can also alter the transcription and translation of genes such as hsp70, myc, jun, and fos (20)(21)(22)(23).…”

mentioning

confidence: 99%

Effect of electromagnetic field exposure on chemically induced differentiation of friend erythroleukemia cells.

Chen

Upham

Sun

et al. 2000

Environ Health Perspect

View full text Add to dashboard Cite

Whether exposure of humans to extremely low frequency electromagnetic fields (ELF-EMF) can cause cancer is controversial and therefore needs further research. We used a Friend erythroleukemia cell line that can be chemically induced to differentiate to determine whether ELF-EMF could alter proliferation and differentiation in these cells in a manner similar to that of a chemical tumor promoter. Exposure of this cell line to 60 Hz ELF-EMF resulted in a dose dependent inhibition of differentiation, with maximal inhibition peaking at 40% and 40 mG (4 microT). ELF-EMF at 10 mG (1.0 microT) and 25 mG (2.5 microT) inhibited differentiation at 0 and 20%, respectively. ELF-EMF at 1.0 (100) and 10.0 G (1,000 microT) stimulated cell proliferation 50% above the sham-treated cells. The activity of telomerase, a marker of undifferentiated cells, decreased 100[times] when the cells were induced to differentiate under sham conditions, but when the cells were exposed to 0.5 G (50 microT) there was only a 10[times] decrease. In summary, ELF-EMF can partially block the differentiation of Friend erythroleukemia cells, and this results in a larger population of cells remaining in the undifferentiated, proliferative state, which is similar to the published results of Friend erythroleukemia cells treated with chemical-tumor promoters.

show abstract

Signal perception and transduction: the role of protein kinases

Cited by 190 publications

References 167 publications

Tocopheryl Succinate—Versatile Functions due to Its Unique Physicochemical Properties

Tocopheryl Succinate—Versatile Functions due to Its Unique Physicochemical Properties

Activation of protein kinase C promotes human cancer cell growth through downregulation of p18INK4c

Effect of electromagnetic field exposure on chemically induced differentiation of friend erythroleukemia cells.

Contact Info

Product

Resources

About