Phosphorylation events, regulation

In order to determine what phosphorylation event(s) might lead to regulation of the channels by PKA, studies of the phosphorylation of the channel subunits have... 

In the x-ray structure of rhodopsin, an amphipathic helix runs parallel to the membrane from the intracellular end of TM-VII beneath the seven-helical bundle to the other side of TM-I and TM-II. At this point, one or more Cys residues are often found and are known to be subject to a dynamic posttranslational modification with palmitic acid residues. Like the phosphorylation event, the palmitoylation process appears to be dynamically regulated by receptor occupancy and is also involved in the desensitization phenomenon. The two posttranslational modifications can influence each other. For example, the conformational constraint induced by palmitoylation may alter the accessibility of certain phosphorylation sites. Like the phosphorylation process, the functional consequences of palmitoylation also appear to vary from receptor to receptor. 

Proteasome activity can also be regulated by phosphorylation. For example, Yang et al have shown that phosphorylation events are necessary for the assembly of the 26S proteasome. Several subunits including MSSl, S4, S6, and S12 of the 19S RC have been shown to be phosphorylated. Recently it bas been demonstrated that assembly of the proteasome requires phosphorylation of Rpt6, an ATPase subunit. ... 

The mitogenic activated protein kinase (MAPK) downstream from the Ras protein is organized in modules containing three types of protein kinases, which are successively activated by sequential phosphorylation events. The cell contains different MAPK modules, which differ in the nature of the triggering stimuli and the nature and specificity of the protein kinase components. The signal transducing function of a MAPK pathway is thus determined by the nature of the MAPK module involved this, in turn, depends on the properties of the protein kinases it contains, which differ in regulation and substrate specificity. The exact composition of the MAPK module is not fixed rather, different subtypes of protein kinase may be recruited to a module in a variable... 

In addition to regulation involving quantitative changes in protein levels, we have identified at least one apparent psi protein phosphorylation event (Fig. 7). This high molecular weight phosphoprotein appears early in Pi starvation and is not excreted into the medium. The function of this molecule in psi metabolism is unknown. 

Figure 2. Schematic representation of the activation of the cdk4/cyclin D complex during Gl. Evidence shows that CaMKIa, which can be activated by either CaMKKa or (3, activates the cdk4/cyclin D complex, leading to the phosphorylation of Rb and therefore de-repression of E2F transcription factor members. The mechanism by which CaMKI regulates cdk4/cyclin D remains to be determined. GFR, receptor for a growth factor CAK, cdk activating kinase p21/p27, members of the inhibitory Cip and Kip families, respectively E2F 1-3, transcription factors 1-3 of die E2F family Rb, Retinoblastoma protein P, phosphorylation event...

Figure 3 The MARK cascade. A signaling cascade generally refers to a series of enzyme modification processes, as in the activation of extracellular signal-regulated kinase (Erk) isoforms, which are mammalian mitogen-activated protein kinases (MAPKs). The first kinase, Raf, is activated (indicated by an asterisk) by numerous inputs, allowing it to phosphorylate MEK on two sites Erk is phosphorylated dually in a similar fashion by MEK. Each phosphorylation event is thought to require a separate encounter between enzyme and substrate, which gives rise to interesting dynamical properties. Not depicted here, but equally important, are the phosphatases that catalyze the reverse reactions.

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