Cell function receptor phosphorylation

Heterologous desensitisation refers to the desensitisation of the response to one agonist by the application of a different agonist. For example, desensitisation of a response to adrenaline by application of 5-HT is mediated by protein kinase A or protein kinase C because these kinases can phosphorylate receptors which are not occupied by agonist. Phosphorylation disrupts the receptor-G-protein interaction and induces the binding of specific proteins, arrestins which enhance receptors internalisation via clathrin-coated pits. Thus desensitisation of G-protein-coupled receptors results in a decrease in the number of functional receptors on the cell surface. 

Schmidt I don t know whether I can answer the why question, but the how question has a conceptual framework to build it around. What you are looking for is some kind of phosphorylation target of cyclin B that is a non-cell cycle functioning receptor. You are looking for some cell cycle receptor sitting in the membrane that cyclin B goes over to, puts the phosphate on, activates it and says now I am receptive . 

JAKs and signal transducers and activators of transcription (STATs) are functionally analogous with IRS and PI3K. JAKs are physically associated with a cell surface receptor (e.g. for leptin, erythropoietin (EPO), growth factors or cytokines) STATs are free monomeric proteins within the cytosol but following phosphorylation by a JAK, individual proteins dimerize and then move into the nucleus of the cell where they control gene expression. 

The insulin receptor protein represents a ligand-operated enzyme (C), a catalytic receptor. When insulin binds to the extracellular attachment site, a tyrosine kinase activity is "switched on at the intracellular portion. Protein phosphorylation leads to altered cell function via the assembly of other signal proteins. Receptors for growth hormones also belong to the catalytic receptor class. 

As a part of our program to develop new adjuvants for the into-cell delivery of phosphorylated nucleotide-type antiviral agents (see Section 3 of this chapter), we became interested in developing a sapphyrin-based approach to phosphate anion chelation. As proved true for halide anion recognition, important initial support for the idea that sapphyrins could function as phosphate anion receptors came from single crystal X-ray diffraction studies. In fact, to date, five X-ray structures of sapphyrin-phosphate complexes have been obtained. ... 

In this reaction chain, ZAP kinase performs an essential function. Tlie phosphorylated ARAM motives recruit ZAP70 kinase to the T cell receptor complex and mediate high affinity binding to the kinase. The two SH2 domains of ZAP70 kinase bind in tandem fashion to the twice-phosphorylated ARAM motif ZAP70 kinase shows a complex pattern of Tyr phosphorylation, including phosphorylations with an inhibitory effect. 

The protein kinase family encompasses more than three hundred members of critically important enzymes, each one with a specific role or function within the cell. These enzymes, ATP-phosphotransferases, recognize target proteins and through the phosphorylation of specific sites either activate or deactivate a particular pathway of signal transduction. Many of these signaling pathways are associated with cell surface receptors, which are located in the membranes that surround cells. The difference between the families of protein kinases is that they have different targets and generally fall into two major classes ... 

Cytokines all function using a group of transmembrane receptors embedded in the plasma membranes of target cells. The receptors have no tyrosine kinase activity but associate with and activate kinases known as Janus kinases (JAKs). These kinases phosphory-late tyrosine side chains in their receptors, and the phosphorylated receptors activate transcription factors of the STAT (signal transducer-activators of transcription) group.186-195 The specificity of cytokine action results from a combination of receptor recognition and recognition of the various STAT molecules by different JAKs.111 Cytokines have a variety of structures. Many are helix bundles or have (3 sheet structures (Fig. 30-6). 

Tyrosyl phosphorylation of the solubilized insulin receptor also appears to affect its functioning per se, in that autophosphorylation leads to an increase in the receptor tyrosyl kinase activity expressed towards exogenous substrates [68]. As autophosphorylation occurs at multiple sites on the j8 subunit it will be necessary to determine which of these sites are of regulatory significance. Such studies require that results obtained using solubilized receptor preparations be compared with those using intact cells where tyrosyl phosphorylation of the receptor appears to be very small in comparison with the phosphorylation of the receptor on serine residues [69]. 

Stephens, L., McGregor, A., and Hawkins, P., 2000, Phosphoinositide 3-kinases Regulation by cell-surface receptors and function of 3-phosphorylated lipids. In S. Cockcroft (ed.), Frontiers in Molecular Biology, Vol. 27, Biology of phosphoinositides. Oxford University Press, New York, pp. 32-108. 

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