Kinases second messenger-dependent

Heterologous desensitization is a form of desensitization which does not require agonist binding of the receptor. Second messenger dependent kinases such as protein kinase A (PKA) and protein kinase C (PKC) are involved in this form of receptor desensitization. Heterologous desensitization simply depends on the overall kinase activity which is regulated by many different stimuli. 

Diverse actions of extracellular signals are mediated by second-messenger-dependent protein kinases 396... 

Second-messenger-dependent Protein kinase A (cAMP kinase)... 

The mitogen-activated protein kinase cascade is second-messenger-independent. Although the second-messenger-dependent protein kinases were identified first as playing an important role in neuronal function, we now know that many other types of protein serine-threonine kinase are also essential (Table 23-1). Indeed, one of the most critical discoveries of the 1990s was the delineation of the mitogen-activated protein kinase (MAP kinase or MAPK) cascades. 

Second-messenger-dependent kinases, such as cAMP-dependent protein kinase A (PKA) and protein kinase C (PKC), are most often implicated in heterologous desensitization (123,129) however, the systems involved may vary between cell types (130). These protein kinases are associated with GPCR desensitization that... 

Figure 5.3 shows how the second messenger, cAMP, formed fi om ATP by adenylyl cyclase, transmits the signal by activating a second-messenger-dependent serine/ threonine protein kinase, the cyclic AMP-dependent protein kinase A (PKA). 

Another second-messenger-dependent kinase which interacts with targeting proteins, is the cAMP-dependent protein kinase A. PKA interacts with AKAPs (A-kinase-associated proteins). AKAPs bind to the dimeric form of the regulatory subunit of PKA. They are multivalent linkers, which bind not only to PKA, but also to other kinases, such as PKC, and the Ca +Z calmodulin-dependent kinase II and the phosphatase PP2B (Fig. 7.6). 

Usually, PKs are activated by second messengers and they are often named after these second messengers (cAMP-dependent PK for example). However, there are also other types of PKs that are not second-messenger-dependent. Among these are protein tyrosine kinases (which phosphorylate substrate proteins specifically on tyrosine residues), casein kinases, and numerous others. - ... 

Group II assays consist of those monitoring cellular second messengers. Thus, activation of receptors to cause Gs-protein activation of adenylate cyclase will lead to elevation of cytosolic or extracellularly secreted cyclic AMP. This second messenger phosphorylates numerous cyclic AMP-dependent protein kinases, which go on to phosphorylate metabolic enzymes and transport and regulatory proteins (see Chapter 2). Cyclic AMP can be detected either radiometrically or with fluorescent probe technology. 

Cyclic nucleotides (cAMP and cGMP) are formed enzymatically from the corresponding triphosphates. As ubiquitous second messengers, they mediate many cellular functions which are initiated by first (extracellular) messengers. Their prime targets in eucaryotic cells are protein kinases ( cyclic AMP-dependent protein kinase, cyclic GMP-dependent protein kinase), ion channels and ensymes. 

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