Regulation of nuclear phospholipase C activity

A body of evidence, linking inositide-specific phospholipase C (PI-PLC) to the nucleus, is quite extensive. The main isoform in the nucleus is PI-PLCβ1, whose activity is up-regulated in response to insulin-like growth factor-1 (IGF-1) or insulin stimulation. Whilst at the plasma membrane this PI-PLC is activated and regulated by Gαq/α11 and Gβg subunits, there is yet no evidence that qα/α11 is present within the nuclear compartment, neither GTP-γ-S nor AlF4 can stimulate PI-PLCβ1 activity in isolated nuclei. Here we review the evidence that upon occupancy of type 1 IGF receptor there is translocation to the nucleus of phosphorylated mitogen-activated protein kinase (MAPK) which phosphorylates nuclear PI-PLCβ1 and triggers its signalling, hinting at a separate pathway of regulation depending on the subcellular location of PI-PLCβ1. The difference in the regulation of the activity of PI-PLCβ1mirrors the evidence that nuclear and cytoplasmatic inositides can differ markedly in their signalling capability. Indeed, we do know that agonists which affect nuclear inositol lipid cycle at the nucleus do not stimulate the one at the plasma membrane

Effects of an extremely large flood on the bed of a steep mountain stream.

This presentation reports about a very large flood (20-30 years return time interval) that markedly affected teh step-pool geomorphology of the streambed of a steep mpuntain stream. The geomorphic parameters and data of the step-pool sequences before the flood are compared with those after the flood. Importnat changes were observed. They include teh widening of teh step-stpe wave length, the removal of old steps and the generaion of the of new ones. The stream bed re-organisation induced by such a big flood is anlysed

Nuclear protein kinase C isoforms: key players in multiple cell functions?

Protein kinase C (PKC) isozymes are a family of serine/threonine protein kinases categorized into three subfamilies: classical, novel, and atypical. PKC isozymes, whose expression is cell type-specific and developmentally regulated, are key transducers in many agonist-induced signaling cascades. To date at least 10 different PKC isotypes have been identified and are believed to play distinct regulatory roles. PKC isoforms are catalytically activated by several lipid cofactors, including diacylglycerol. PKC is thought to reside in the cytoplasm in an inactive conformation and to translocate to the plasma membrane or cytoplasmic organelles upon cell activation by different stimuli. However, a sizable body of evidence collected over the last 15 years has shown PKC to be capable of translocating to the nucleus. Furthermore, PKC isoforms can reside within the nucleus. Studies from independent laboratories have to led to the identification of several nuclear proteins which act as PKC substrates as well as to the characterization of some nuclear PKC-binding proteins which may be of fundamental importance for finely tuning PKC function in this peculiar cell microenvironment. Most likely, nuclear PKC isozymes are involved in the regulation of several important biological processes such as cell proliferation and differentiation, neoplastic transformation, and apoptosis. In this review, we shall summarize the most intriguing evidence about the roles played by nuclear PKC isozymes

Nuclear phospholipase C signaling through type 1 IGF receptor and its involvement in cell growth and differentiation

The existence of a nuclear polyphosphoinositol metabolism, independent from that at the plasma cell membrane, is now widely recognized. Specific changes in the nuclear phosphatidylinositol (PtdIns) metabolism have been implicated in cell growth, differentiation and neoplastic transformation. Here, the main features of nuclear inositol lipid signaling through type I IGF receptor, is reviewed with particular attention to the role of inositide-specific phospholipase C (PI-PLC) beta 1 in cell proliferation and differentiation, due to the peculiar localization of this molecule in the nuclear compartment

Involvement of the phosphoinositide 3-kinase/Akt signaling pathway in the resistance to therapeutic treatments of human leukemias

A major factor undermining successful cancer treatment is the occurrence of resistance to conventional treatments such as chemotherapy and ionizing radiation. Evidence accumulated over the recent years has indicated the phosphoinositide 3-kinase/Akt signal transduction pathway as one of the major factors implicated in cancer resistance to conventional therapies. Indeed, the phosphoinositide 3-kinase/Akt axis regulates the expression and/or function of many anti-apoptotic proteins which strongly contributes to cancer cell survival. As a result, small molecules designed to specifically target key components of this signaling network are now being developed for clinical use as single therapeutic agents and/or in combination with other forms of therapy to overcome resistance. Initially, the phosphoinositide 3-kinase/Akt signal transduction pathway has been mainly investigated in solid tumors. Recently, however, this network has also been recognized as an important therapeutic target in human leukemias. Specific inhibition of this signalling pathway may be a valid approach to treat these diseases and increase the efficacy of standard types of therapy