G-protein receptor kinase

The carboxy terminus of the ft receptor was essential for agonist-induced desensitization [83, 132] since truncation of the receptor prevented desensitization. Like those findings with the k receptor, the enzyme G protein receptor kinase (GRK) appears to be involved in the desensitization process, since blockade of GRK prevented the desensitization process. Wang [132] has proposed that GRK catalyzes the phosphorylation of a series of serine/threonine residues in the C-terminus of the fi receptor to desensitize the receptor. 

Agonist-dependent desensitization of the kappa opioid receptor by G protein receptor kinase and beta-arrestin. J Biol Chem 1999 274 233802-233807. 

CDK, cyclin-dependent kinase ERK, extracellular signal-regulated kinase GRK, G protein receptor kinase JNK, Jun kinase MAP kinase, mitogen activated protein kinase MEK, MAP kinase and ERK kinases RSK, ribosomal S6 kinase, GSK, glycogen synthase kinase SAPK, stress-activated protein kinase SEK, SAPK kinase. 

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. 

Other mechanisms have also been implicated in odor adaptation, including cAMP-dependent phosphorylation of ciliary proteins via protein kinase A G-protein-receptor kinase activity (GRK3), possibly via phosphorylation of the OR Ca2+/calmodulin kinase II (CaMKII) phosphorylation of ACIII cGMP and carbon monoxide [ 31 ]. These latter three mechanisms have been particularly linked to longer-lasting forms of adaptation, on the order of tens of seconds (for CaMKII) or minutes (CO/cGMP). Together with the short-term adaptation described above, these various molecular mechanisms provide the OSN with a number of ways to fine-tune odor responses over time. 

EFTU eukaryotic elongation factor GRK G protein receptor kinase... 

In additional studies, it was demonstrated that norepinephrine can induce at least two conformational states in the (32-AR one capable of activating Gs and another required for interaction of the receptor with G protein-receptor kinase (GRK) or arrestin and hence agonist-induced internalization (S3). In contrast, dopamine, which can stimulate Gs activation of the (32-AR but not internalization, induced only one of the conformational states observed with norepinephrine (83). 

Ping P, Anzai T, Gao M, Hammond HK. Adenylyl cyclase and G protein receptor kinase expression during development of heart failure. Am J Physiol 1997 273 H707-H717. 

Expression of receptors in cells containing different G-protein, G-protein receptor kinases, and other proteins that modify GPCR signaling can result in abnormal drug-receptor behavior (6). Such changes result in cellular responses in screening efforts that identify hits that do not translate to nontransfected cells, and most importantly, humans. 

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