Hydrolysis of inositol phospholipids by phospholipase C is initiated by either receptor stimulation or opening of Ca2+ channels. This was once thought to be the sole mechanism to produce the diacylglycerol that links extracellular signals to intracellular events through activation of protein kinase C. It is becoming clear that agonist-induced hydrolysis of other membrane phospholipids, particularly choline phospholipids, by phospholipase D and phospholipase A2 may also take part in cell signaling. The products of hydrolysis of these phospholipids may enhance and prolong the activation of protein kinase C. Such prolonged activation of protein kinase C is essential for long-term cellular responses such as cell proliferation and differentiation.

https://science.sciencemag.org/content/sci/258/5082/607.full.pdf

Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C

Sixteen years have passed since the description of the nuclear factor-кB (NF-кB) as a regulator of к light-chain gene expression in murine B lymphocytes (Sen & Baltimore, 1986a) During that time, over 4,000 publications have appeared, characterizing the family of Rel/NF-кB transcription factors involved in the control of a large number of normal and pathological cellular processes The physiological functions of NF-кB proteins include immunological and inflammatory responses, developmental processes, cellular growth and modulating effects on apoptosis In addition, these factors are activated in a number of diseases, including cancer, arthritis, acute and chronic inflammatory states, asthma, as well as neurodegenerative and heart diseases

Activators and target genes of Rel/NF-kappaB transcription factors.

Publisher Summary The chapter introduces the mitogen-activated protein (MAP) kinase (MAPK) module. The identification of MAP kinase pathways exemplifies the power of combining biochemical and genetic approaches to molecular problems. The chapter discusses the mammalian MAPK pathways—ERKl/2 and MKKl/2 pathways—and stress-activated protein kinase pathways. The regulation of MAPK pathways by protein phosphatases is discussed in the chapter describing in detail about dual specificity phosphatases, serinenhreonine phosphatases, and protein tyrosine phosphatases. The chapter explores the cellular substrates of MAP kinases, wherein it discusses about protein kinase substrates for MAPKS, nuclear transcription factors, signaling components, and cytoskeletal proteins. Responses to MAPK pathways, regulation of cell growth and transformation, and regulation of cell differentiation and development have also been summarized in the chapter. The chapter describes the yeast MAPK pathways of saccharomyces cerevisiae (Budding Yeast) and Schizosaccharomyces pombe (Fission Yeast). The chapter provides the description of the intracellular targeting and spatial regulation of MAPK pathway components, signaling complexes, and the nuclear translocation of MAPK and MKK. Eukaryotic MAPK cascades provide excellent examples of signal transduction mechanisms that embody key principles common to many, if not all, signaling pathways. Many fundamental questions remain for future studies to investigate the mechanisms by which these pathways are regulated as well as the cellular responses that they control.

Signal transduction through MAP kinase cascades.

A novel arachidonic acid-selective cytosolic PLA2 contains a Ca2+-dependent translocation domain with homology to PKC and GAP

Membrane lipid composition and cellular function.

Raf-1 kinase possesses distinct binding domains for phosphatidylserine and phosphatidic acid. Phosphatidic acid regulates the translocation of Raf-1 in 12-O-tetradecanoylphorbol-13-acetate-stimulated Madin-Darby canine kidney cells.

A novel mechanism of diglyceride formation. 12-O-tetradecanoylphorbol-13-acetate stimulates the cyclic breakdown and resynthesis of phosphatidylcholine.

Larry W. Daniel

Papers

Raf-1 kinase possesses distinct binding domains for phosphatidylserine and phosphatidic acid. Phosphatidic acid regulates the translocation of Raf-1 in 12-O-tetradecanoylphorbol-13-acetate-stimulated Madin-Darby canine kidney cells.

A novel mechanism of diglyceride formation. 12-O-tetradecanoylphorbol-13-acetate stimulates the cyclic breakdown and resynthesis of phosphatidylcholine.

Evidence of protein kinase C involvement in phorbol diester-stimulated arachidonic acid release and prostaglandin synthesis.

Choline-linked Phosphoglycerides A SOURCE OF PHOSPHATIDIC ACID AND DIGLYCERIDES IN STIMULATED NEUTROPHILS*

1-beta-D-Arabinofuranosylcytosine stimulates ceramide and diglyceride formation in HL-60 cells.