3-Adrenergic receptor kinase

E. G protein-conpled receptors /3-Adrenergic receptor kinase (BARK) Rhodopsin kinase II. Ser/Thr/Tyr protein kinases MAP kinase kinase (MAPK kinase) —TEY— phosphorylation by... 

Some of these protein kinases are specific for particular receptors (e.g., 3-adrenergic receptor kinase [pARK], now referred to as GRK2). 

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. 

Dawson, T. M., Arriza, J. L., Jaworsky. D. E., etal. (1993). /3-Adrenergic receptor kinase-2 and /3-arrestin-2 as mediators of odorant-induced desensitization. Science 259,825-829. 

Parruti, G. Ambrosini, G. Sallese, M. De Blasi, A. Molecular cloning, functional expression and mRNA analysis of human /3-adrenergic receptor kinase 2. Biochem. Biophys. Res. Commun., 190, 475-481 (1993)... 

Ungerer, M. Kessebohm, K. Kronsbein, K. Lohse, M.J. Richardt, G. Activation of )3-adrenergic receptor kinase during myocardial ischemia. Circ. Res., 79, 455-460 (1996)... 

The phenomenon is called desensitization or adaptation. It allows the system to adapt to a given level of hormone so that it can respond to changes in hormone concentrations rather than to absolute amounts. Desensitization is effected by phosphorylation by 3-adrenergic receptor kinase at multiple seine and threonine sites on the carboxyl-terminal region of the P-adrenergic receptor when it has epinephrine bound to it. These covalent modifications of the hormone-receptor complex allow P-arrestin to bind it and further inhibit, but not completely prevent, the GDP-GTP exchange. These events thereby decrease the activation of adenylate cyclase. However, the desensitized receptor can still respond to an increase in epinephrine concentrations. Ultimately, a phosphatase reverses the effects of the modification and resensitizes the receptor. 

---