Signal transduction other kinases

The EPO receptor is a member of the haemopoietic cytokine receptor superfamily. Its intracellular domain displays no known catalytic activity, but it appears to couple directly to the JAK2 kinase (Chapter 8) that likely promotes the early events of EPO signal transduction. Other studies have implicated additional possible signalling mechanisms, including the involvement of G proteins, protein kinase C and Ca2+. The exact molecular events underlining EPO signal transduction remain to be elucidated in detail. 

Occurrence profiles involving functions, pathways, and other genomic data are used in comparative analysis in a way similar to that previously discussed for genes. For example, occurrence or abundance profiles of certain COGs (such as signal transduction histidine kinase, serine/threonine protein kinase, and phosphatase) can provide a broad overview of protein families present or absent in the genomes of interest, whereas occurrence profiles of Pfam domains found in these proteins could provide additional information on the signals sensed by the proteins. 

Other enzymes present in myelin include those involved in phosphoinositide metabolism phosphatidylinositol kinase, diphosphoinositide kinase, the corresponding phosphatases and diglyceride kinases. These are of interest because of the high concentration of polyphosphoinositides of myelin and the rapid turnover of their phosphate groups. This area of research has expanded towards characterization of signal transduction system(s), with evidence of G proteins and phospholipases C and D in myelin. 

FIGURE 14-6 Main signaling pathways for histamine receptors. Histamine can couple to a variety of G-protein-linked signal transduction pathways via its four different receptors. The Hj receptor activates the phosphatidylinositol turnover via Gq/11 proteins. The other receptors either positively (H2 receptor) or negatively (H3 and H4 receptor) regulate adenylyl cyclase activity via Gs and GUo protein activation respectively. Several additional signaling pathways have been described, which are not shown. Abbreviations PfP2, phosphatidylinositol 4,5-bisphosphate PIC, phospholipase C AC, adenylyl cyclase ATP, adenosine triphosphate cAMP, cyclic AMP PKC, protein kinase C PICA, protein kinase A. 

The brain contains many other types of second-messenger-independent protein kinases. Examples of other second-messenger-independent protein kinases are listed in Table 23-1. Many of these include enzymes that were identified originally in association with a particular substrate protein but shown later to play a more widespread role in brain signal transduction. The functional role of one of these, [3-adrenergic receptor kinase (PARK), a type of G protein receptor kinase (GRK), is discussed further below. 

RING finger proteins may have other domains associated with signal transduction, such as SH3 and STAT domains and domains that bind and effect hydrolysis of nucleotides in signal transduction or for other purposes. These include ATPases, ATP synthases, serine/threonine kinases, GTP-binding domains, ADP-ribosylation domains and AAA-superfamily ATPases (http //home.cancer.gov/lpds/weissman). 

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