Receptor-associated protein

Most protein serine-threonine kinases undergo autophosphorylation. The autophosphorylation of most protein kinases is associated with an increase in kinase activity [4, 10]. In some instances, such as with the RII subunit of PKA, autophosphorylation represents a positive feedback mechanism for kinase activation, in this case by enhancing the rate of dissociation of the RII and C subunits. In the case of CaMKII, autophosphorylation causes the catalytic activity of the enzyme to become independent of Ca2+ and calmodulin. This means that the enzyme, activated originally in response to elevated cellular Ca2+, remains active after Ca2+ concentrations have returned to baseline. By this mechanism, neurotransmitters that activate CaMKII can produce relatively long-lived alterations in neuronal function. In other instances, such as with the receptor-associated protein tyrosine kinases (discussed in Ch. 24), autophosphorylation is an obligatory step in the sequence of molecular events through which those kinases are activated and produce physiological effects. 

Regulation of neurotransmitter receptors the p-adren-ergic receptor. This receptor, of which three subtypes have been cloned, mediates many of the effects of norepinephrine and epinephrine in the brain and peripheral tissues. One of the dramatic features of P-adrenergic receptor function is its rapid desensitization in response to agonist stimulation. It is now known that one important mechanism for this desensitization is phosphorylation of the receptor both by PKA and by a receptor-associated protein kinase, PARK (also called GRK2 Fig. 23-6). 

Medved, L.V., M. Migliorini, I. Mikhailenko, L.G. Barrientos, M. Llinas, and D.K. Strickland. 1999. Domain organization of the 39-kDa receptor-associated protein. J Biol Chem 274 111-121. 

Wang H, Bedford FK, Brandon NJ, Moss SJ, Olsen RW. 1999. GABAA receptor-associated protein links GABAa receptors and the cytoskeleton. Nature 397 69-72. 

Rodig SJ, Rutok IL, Paterson IC et al (2010) The pre-B-cell receptor associated protein VpreBS is a useful diagnostic marker for identifying c-MYC translocated lymphomas. Haematologica 95 2056-2062... 

Growth hormones, important in diabetes and cancer, activate a receptor with an intrinsic intracellular tyrosine protein kinase activity that passes on the signal by phosphorylating other proteins, often kinases themselves. To date, no specific second messengers have been associated with these systems. The amplification occurs by the turn-on of the receptor-associated protein kinase activity that can phosphorylate many proteins. 

Key Words Serotonin 5-HT receptor 5-HT receptor-associated protein receptosome trafficking targeting signaling. 

Regnier, C. H., Tomasetto, C., Moog-Lutz, C., Chenard, M. P., Wendling, C., Basset, P., and Rio, M. C. (1995). Presence of a new conserved domain in CARTl, a novel member of the tumor necrosis factor receptor-associated protein family, which is expressed in breast carcinoma./. Biol. Chem. 270, 25715—25721. 

J. D. Fondell, M. Guermah, S. Malik, and R G. Roeder. Thyroid hormone receptor-associated proteins and general positive cofactors mediate thyroid hormone receptor function in the absence of the TATA box-binding protein-associated factors of TFIID. Proc Nad Acad. Sci, VSA, 96 (5), 1959-1964, 1999. 

Killer cell-activating receptor-associated protein Kilobase... 

Tumor necrosis factor receptor-associated protein with death domain, an adapter protein that recruits other proteins to the cytoplasmic TNF (tumor necrosis factor) receptor complex, involved in apoptosis... 

---