Phosphorylation, receptor subunit

Figure 11.7 Presumed arrangement of GABAa receptor subunits to form a receptor-channel complex, (a) Diagrammatic representation of an individual subunit with four transmembrane regions, extracellular sites for glycosylation and a site for phosphorylation on the intracellular loop between M3 and M4. (b) Association of five subunits to form a central ionophore bounded by the M2 region of each subunit. The suggested stoichiometry of the most widely expressed form of receptor is 2a, 2 and ly. Shown below are the possible subunit combinations of one such benzodiazepine-sensitive receptor together with a benzodiazepine-insensitive receptor in which the 7 subunit is replaced by a c5, and a ti-containing receptor with four different subunit types...

There is evidence that multiple kinases can phosphorylate several GABAa receptor subunits, to alter GABAergic activity in the brain (Browning et al. 1993 Poisbeau et al. 1999). Depending on the brain area and /or the receptor subunits involved, phosphorylation by kinases can result in either activation or inhibition... 

Our working hypothesis is that subunit stoichiometry or changes in the structure of individual receptor subunits give rise to the different conductance subtypes and that phosphorylation by the different kinase enzymes has major effects on the P-open values of the receptor. Should the hypothesis hold, then alterations in the phosphorylation state of the receptor by the different kinase enzymes may (as stated earlier) be important in the development of anthelmintic resistance. 

Hallett, P. J., Spoelgen, R., Hyman, B. T., Standaert, D. G. and Dunah, A. W. (2006). Dopamine D1 activation potentiates striatal NMDA receptors by tyrosine phosphorylation-dependent subunit trafficking. J. Neurosci. 26, 4690-700. 

GRIP, PICK1 and PSD95 also interact with kainate receptor subunits GluR5 and 6. PKC, which binds to PICK1, may phosphorylate these subunits, thereby causing them to anchor more stably at the synapse, a mechanism that could strengthen kainate receptor-mediated transmission. 

Lau, L. F. and Huganir, R. L. Differential tyrosine phosphorylation of N-methyl-D-aspartate receptor subunits. /. Biol. Chem. 270 20036-20041,1995. 

Moon, I. S., Apperson, M. L. and Kennedy, M. B. The major tyrosine-phosphorylated protein in the postsynaptic density fraction is N-methyl-D-aspartate receptor subunit 2B. Proc. Natl Acad. Sci. U.S.A. 91 3954-3958,1994. 

Tezuka, T., Umemori, H., Akiyama, T. et al. PSD-95 promotes Fyn-mediated tyrosine phosphorylation of the N-methyl-D-aspartate receptor subunit NR2A. Proc. Natl Acad. Sci. U. S. A. 96 435-440,1999. 

Kimura T., Sakamoto, H., Appella, E., and Siraganian, R.P. 1997. The negative signaling molecule SH2 domain containing inositol polyphosphate 5-phosphatase (SHIP) binds to the tyrosine phosphorylated P subunit of the high affinity IgE receptor. J. Bio.Chem. 272 ... 

Various hormonal agents (eg, glucocorticoids) lower the affinity of insulin receptors for insulin growth hormone in excess increases this affinity slightly. Aberrant serine and threonine phosphorylation of the insulin receptor subunits or IRS molecules may result in insulin resistance and functional receptor down-regulation. 

Zheng, X., Zhang, L., Wang, A. p., Bennett, M. V. L., Zukin, S. Protein kinase C potentiation of N-methyl-D-aspartate receptor activity is not mediated by phosphorylation of N-methyl-D-aspartate receptor subunits, Proc. Natl. Acad. Sci. USA 1999, 96, 15262-15267. 

Seidenman K. J., Steinberg J. P., Huganir R., and Malinow R. (2003). Glutamate receptor subunit 2 Serine 880 phosphorylation modulates synaptic transmission and mediates plasticity in CA1 pyramidal cells. J. Neurosci. 23 9220-9228. 

To examine the phosphorylation of the myc-tagged wild-type 5-HT3A receptor subunits from the guinea pig, stably transfected HEK 293 cells were meta-bolically labeled with [32P]phosphoric acid (158). It was demonstrated that both splice variants of the 5-HT3A receptor subunit were phosphorylated. Moreover, site-specific mutagenesis revealed that phosphorylation occurs at Ser409, a potential target of PKA. 

Esteban JA, Shi SH, Wilson C, Nuriya M, Huganir RL, Malinow R (2003) PKA phosphorylation of AMPA receptor subunits controls synaptic trafficking underlying plasticity. Nat Neurosci 6 136-143. 

Nakazawa, K., Mikawa, S., Hashikawa, T., and Ito, M. (1995). Transient and persistent phosphorylation of AMPA-type glutamate receptor subunits in cerebellar Purkinje... 

Signalling by G-protein-coupled receptors is terminated by binding of the receptor kinase to the receptor, followed by phosphorylation. Receptor kinases are serine/threonine kinases, recognizing the active conformation of the receptor. A carrier function is attributed to Py-subunits in bringing the kinase to the receptor in the membrane. 25 For that function, isoprenylation of the Py-complex is required. This function is comparable to that of Ras, bringing the cytosolic Raf kinase to the membrane for activation. Both the y-subunits of the Py-complex and Ras are modified by prenylation (see Chapter 3). Control of G proteins by RGS proteins... 

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