Cytoplasm nuclear interactions

Fig. 4.3 Pouyssegur and colleagues found that in the resting dormant state of a cell (a) the MAP kinases are kept in the cytoplasm by interaction with the upstream cytosolic kinases of the MAP kinase cascade, (b) Activation of the MAP kinase cascade by a growth factor uncouples the MAPK from upstream MAPKKs and initiates translocation of MAPK to the nucleus, where it signals entry into the S phase of the cell cycle. In the nucleus, MAPK is retained by short-lived nuclear anchoring proteins. When their proteolytic removal is blocked, the residence time of MAPK in the nucleus is prolonged.

Fig. 4.8. Major classes of drug receptors. (A) Transmembrane ligand-gated ion channel receptor. (B) Transmembrane G protein-coupled receptor (GPCR). (C) Transmembrane catalytic receptor or enzyme-coupled receptors. (D) Intracellular cytoplasmic/nuclear receptor. (From Simon JB, Golan DE, Tashjian A, Armstrong E, et al., eds. Chapter 1, Drug-Receptor Interactions. In Principles of Pharmacology The Pathophysiologic Basis of Drug Therapy. Baltimore Lippincott Williams Wilkins, 2004, pp. 3-16, with permission.)...

The NHR contains also the conserved Calcineurin docking site, PxlxIT, required for the physical interaction of NEAT and Calcineurin. Dephosphorylation of at least 13 serines residues in the NHR induces a conformational change that exposes the nuclear localization sequences (NLS), allowing the nuclear translocation of NEAT. Rephosphorylation of these residues unmasks the nuclear export sequences that direct transport back to the cytoplasm. Engagement of receptors such as the antigen receptors in T and B cells is coupled to phospholipase C activation and subsequent production of inositol triphosphate. Increased levels of inositol triphosphate lead to the initial release of intracellular stores of calcium. This early increase of calcium induces opening of the plasma membrane calcium-released-activated-calcium (CRAC) channels,... 

In the case of the ER, when a region of 20 amino acids between 250 and 270 is missing, the receptor is located strictly in the cytoplasm. Domains of similar size and function have also been located in the receptors of glucocorticoids and of progesterone. The zone of nuclear location overlaps with one of the sequences for interacting with hsp90, which at the same time is next to the DBD. The coincidence of the three functions in a space so restricted implies that they are totally or partly incompatible sterically (Evans 1989 Gruber et al. 2002). 

Ca2+ is the main intracellular signalling molecule in smooth muscle. Fluctuation in local cytoplasmic [Ca2+] near Ca2+-sensitive effector molecules allows for specific regulation of multiple functions. These temporal fluctuations and spatial variations of cytoplasmic [Ca2+] are dependent on the interactions of ion transport proteins located in the plasma membrane (PM) and membranes of the sacoplasmic reticulum (SR), nuclear envelope and mitochondria. These... 

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