Phosphoinositide transduction pathway, role

Very recent efforts to further evaluate the functional implications of phosphoinositol signaling in vertebrate chemosensory transduction have led to the discovery that not only the phosphoinositol breakdown pathway catalyzed by phospholipase C, but also membrane phosphoinositols themselves involving phosphoinositide-3-kinase may play a functional role in the transduction process. It was found that 3-phosphoinositides signaling in concert with the canonical phosphoinositide turnover pathway modulate the cyclic nucleotide signaling cascade downstream of the receptor. The data suggest that 3-phosphoinositide, the primary product of PI3K activity, attenuates the cyclic nucleotide-dependent excitation of olfactory neurons (Spehr et al., 2002). 

In spite of the tongue-in-cheek remarks made above, there is no doubt that the phosphoinositides represent important components of the signal transduction pathway in many cells. As such, the results of investigations of these phospholipids have changed their role as structural components only to a more dignified position as metabolic activist in cells. 

Activation of the chemokine receptor leads to rapid activation of phosphoinositide-spe-cific phospholipases, which leads to inositol-1,4,5-triphosphate formation and a transient rise in intracellular calcium (18). Phospholipase C (PLC) isoforms that are involved in chemokine receptor activation become activated by direct interaction with the J3y subunits. In addition to its interaction with PLCs, the j3y subunits also interact with the type phosphoinositol 3 kinase y (PISKy), and activation of this enzyme results in the formation of PtdIns(3,4,5)P3 (17). Mice that do not express PI3Ky have severely impaired chemo-kine-stimulated signal transduction, and PKB is not activated, suggesting an important role for this pathway in the chemotactic process (27-29). Although leukocytes isolated from these mice showed a decrease in cell chemo-taxis, the response is not completely lost, and under conditions of complete PI3Ky inhibition, neutrophils can still chemotax in response to chemokines (30). 

The next step in the transduction process is more problematical. On the one hand, evidence has been adduced indicating that the ETR protein interacts directly with the CTRl protein kinase [64], On the other hand the rapid effects of ethylene on the activation of SMG proteins suggests that these may play a role in linking the receptor to Raf or other protein phosphorylation cascades, as in the case in animals [65-68], The possible role of such proteins is in itself complex since they may not only control pathways separate from protein phosphorylation cascades (e.g. phosphoinositides [69,70] but may themselves interact via GTPase cascades [71]. Equally, it is important to mention that the small GTP-binding proteins constitute a superfamily, the various members of which may have very different functions [72-77]. In neither Arabidopsis [60] nor in peas [59] is it yet clear which member(s) of the superfamily are activated. 

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