Phospholipase C (EC 3.1.4.11): A malignancy linked signal transduction enzyme

Hongyuan Yang, Fei Shen, Maria Herenyiova, George Weber

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Aim: To elucidate the relationship between phospholipase C, phosphatidylinositol-4,5-bisphosphate (PIP2) phosphodiesterase, EC 3.1.4.11 (PLC) and transformation, progression and proliferation, steady-state activity was determined in a spectrum of transplantable solid rat hepatomas of different growth rates, and in a variety of normal rat organs. Methods. To measure PLC activity in the plasma membrane fraction a standard isotopic method was developed using exogenous PIP2 as substrate. PLC activity was linear with time for 2.5 min and proportional with protein concentrations over a range of 5 to 29 μg per 50 μl reaction mixture. Results. The apparent K(m) for PIP2 was 0.3 mM in both normal liver and rapidly growing hepatoma 3924A. PLC activity in adult rat liver was 747 and 986 nmol/h/mg protein; it increased 1.7- to 2.1-fold in hepatomas of slow an intermediate growth rates and 3.7-fold in rapidly growing hepatoma 3924A. By contrast, no significant difference was observed between 24 hours regenerating and sham-operated livers. PLC activity was high in thymus, spleen, testis, bone marrow, lung, brain, heart and renal cortex, but in the same range in skeletal muscle and liver. PLC has a relatively long half-life as there were no significant changes in PLC specific activity in bone marrow during the 9 hour period after intraperitoneal injection of the protein biosynthetic inhibitor, cycloheximide. PLC was subject to nutritional regulation because at 3 days' starvation the specific activity in rat bone marrow decreased to 78% of control values and recovered after 1-day refeeding. Conclusion: The results indicate that PLC is a transformation- and progression-linked signal transduction enzyme. This work and recent studies showing increased 1-phosphatidylinositol 4-kinase (EC 2.7.1.67) and 1-phosphatidylinositol 4-phosphate-5-kinase (EC 2.7.1.68) provide evidence of a gain in function for a markedly elevated capacity of signal transduction sequence in transplantable rat hepatomas of different growth rates. Inhibition of the activities of kinases and PLC may provide sensitive targets for selective cancer therapy by down-regulating the up-regulated signal transduction cascade.

Original languageEnglish
Pages (from-to)1399-1404
Number of pages6
JournalAnticancer Research
Volume18
Issue number3 A
StatePublished - May 1998

Fingerprint

Type C Phospholipases
Hepatocellular Carcinoma
Signal Transduction
Enzymes
Bone Marrow
Liver
Neoplasms
Growth
1-Phosphatidylinositol 4-Kinase
Phosphoric Diester Hydrolases
Cycloheximide
Protein Sorting Signals
Starvation
Phosphatidylinositols
Intraperitoneal Injections
Recombinant Proteins
Thymus Gland
Half-Life
Testis
Skeletal Muscle

Keywords

  • Enzyme half-life
  • Hepatomas
  • Phospholipase C
  • Regenerating liver

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Yang, H., Shen, F., Herenyiova, M., & Weber, G. (1998). Phospholipase C (EC 3.1.4.11): A malignancy linked signal transduction enzyme. Anticancer Research, 18(3 A), 1399-1404.

Phospholipase C (EC 3.1.4.11) : A malignancy linked signal transduction enzyme. / Yang, Hongyuan; Shen, Fei; Herenyiova, Maria; Weber, George.

In: Anticancer Research, Vol. 18, No. 3 A, 05.1998, p. 1399-1404.

Research output: Contribution to journalArticle

Yang, H, Shen, F, Herenyiova, M & Weber, G 1998, 'Phospholipase C (EC 3.1.4.11): A malignancy linked signal transduction enzyme', Anticancer Research, vol. 18, no. 3 A, pp. 1399-1404.
Yang H, Shen F, Herenyiova M, Weber G. Phospholipase C (EC 3.1.4.11): A malignancy linked signal transduction enzyme. Anticancer Research. 1998 May;18(3 A):1399-1404.
Yang, Hongyuan ; Shen, Fei ; Herenyiova, Maria ; Weber, George. / Phospholipase C (EC 3.1.4.11) : A malignancy linked signal transduction enzyme. In: Anticancer Research. 1998 ; Vol. 18, No. 3 A. pp. 1399-1404.
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