CAMP, protein kinase interactions

II is found on the surface of B cells, neutrophils, and macrophages and shows higher affinity for IL-1 p [7,59]. Types I and II are regulated differently in brain ischemia and may thus play separate roles. In spontaneously hypertensive rats, the mRNA for the type I IL-1 receptor was found to be relatively highly expressed in the normal cortex, with a marked increase 5 days after cerebral ischemia [7,58]. Type II mRNA has low basal expression and a peak 12 hours after the onset of ischemia [7,58]. The possible mechanisms of intracellular signal transduction for IL-1 on peripheral immune cells include effects on cAMP, protein kinase C, and protein phosphorylation. These effects remain to be proved in cerebral ischemia [7,59]. The IL-1-receptor interaction is quickly followed by the induction of immediate-early genes such as c-jun and c-fos [7,60]. 

The eicosanoids have a wide variety of physiologic effects, which are generally initiated through an interaction of the eicosanoid with a specific receptor on the plasma membrane of a target cell (Table 35.4). This eicosanoid-receptor binding either activates the adenylate cyclase-cAMP-protein kinase A system (PGE, PGD,... 

The detailed mechanisms involved in CREB phosphorylation were first established for the cAMP pathway. A first messenger that increases cAMP concentrations leads to activation of PKA and to translocation of the free catalytic subunit of the protein kinase into the nucleus, where it phosphorylates CREB on serine 133. Such phosphorylation then promotes the binding of CREB to a CREB-binding protein (CBP). CBP, upon binding CREB, interacts directly with the RNA polymerase II complex, which mediates the initiation of transcription. In most cases, such interactions lead to the activation of transcription, although it is possible that the expression of some genes may be repressed. 

The cAMP and Ca2+ pathways also interact at the level of protein kinases and protein phosphatases. This is illustrated by inhibitor-1 and DARPP-32, which are phosphorylated and activated by PKA and then inhibit PP1, which can dephosphorylate numerous substrates for Ca2+-dependent protein kinases. Another example is the physical association between PKA and PP2B (a Ca2+/ calmodulin-activated enzyme) via the AKAP-anchoring proteins. 

Ruan, Y., Kotraiah, V., and Straney, D.C., Flavonoids stimulate spore germination in Fusarium solani pathogenic on legumes in a manner sensitive to inhibitors of cAMP-dependent protein kinase, Mol. Plant-Microbe Interact., 8, 929, 1995. 

FIGURE 25. Key interactions in the active site of the cAMP-dependent protein kinase (PKA) the additional H2O hgands on both hexacoordinated ions have been omitted for clarity and the... 

Figure 1.10 Model of a G protein-coupled receptor with 7 membrane-spanning domains. Binding of an agonist to the receptor causes GDP to exchange with GTP. The a-GTP complex then dissociates from the receptor and the py complex and interacts with intercellular en mes or ion channels. The Py complex can activate an ion channel or possibly also interact with intercellular enzymes. GDP, guanine diphosphate GTP, guanine triphosphate cAMP, cyclic adenosine monophosphate PKC, protein kinase C PLC, phospholipase C DAG, diacylglycerol.

Blackmer T, Larsen EC, Bartleson C et al (2005) G protein betagamma directly regulates SNARE protein fusion machinery for secretory granule exocytosis. Nat Neurosci 8 421-5 Boczan J, Leenders AG, Sheng ZH (2004) Phosphorylation of syntaphilin by cAMP-dependent protein kinase modulates its interaction with syntaxin-1 and annuls its inhibitory effect on vesicle exocytosis. J Biol Chem 279 18911-19... 

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