Ca2+/CAM-dependent protein kinase

Ca2+-CaM-dependent Protein Kinase Ca2+-dependent Protein Kinase Central Nervous System... 

Meanwhile, the polar IP3 moiety binds to intracellular receptors on the endoplasmic reticulum, resulting in the liberation of calcium into the cytosol. The calcium binds to calmodulin, which then activates another group of protein kinases (the Ca2+/CaM-dependent protein kinases). Hormonal stimulation can be short-lived because IP3 and DG are rapidly degraded to inactive forms that are ultimately recycled to PIP2 Ca2+ is pumped back into the endoplasmic reticulum, where it is sequestered. 

PHYSIOLOGICAL ROLES OF THE Ca2+/CaM-DEPENDENT PROTEIN KINASE CASCADE IN HEALTH AND DISEASE... 

Joseph, J. D. and Means, A. R., 2000, Identification and characterization of two Ca2- -/CaM-dependent protein kinases required for normal nuclear division in Aspergillus nidulans, J Biol Chem, 275, pp 38230-8. 

The effect of site A phosphorylation in MLCK is to decrease the sensitivity of the enzyme to activation by Ca +/CaM. Though MLCK can be phosphorylated at site A by cAK, protein kinase C (PKC), and the Ca2+/CaM-dependent protein kinase II (CaMK II), the relative importance of these protein kinases in modulating smooth muscle contraction has only recently been defined. 

G protein-coupled receptor kinases (GRKs) 441 scaffold proteins 441 inhibitory G protein (GO 441 calmodulin (CaM) 444 Ca2+/calmodulin-dependent protein kinases (CaM kinases I IV)) 444 two-component signaling systems 452 receptor His kinase 452 response regulator 452 receptorlike kinase (RLK) 455... 

Hanissian, S. H., Frangakis, M., Bland, M. M., Jawahar, S. and Chatila, T. A., 1993, Expression of a Ca2- -/calmodulin-dependent protein kinase, CaM kinase-Gr, in human T lymphocytes. Regulation of kinase activity by T cell receptor signaling, J Biol Chem, 268, pp 20055—63. 

Park, I. K. and Soderling, T. R., 1995, Activation of Ca2+/calmodulin-dependent protein kinase (CaM-kinase) IV by CaM-kinase kinase in Jurkat T lymphocytes, J Biol Chem, 270, pp 30464-9. 

Sakagami, H., Umemiya, M., Kobayashi, T., Saito, S. and Kondo, H., 1999, Immunological evidence that the beta isoform of Ca2 +/calmodulin-dependent protein kinase TV is a cerebellar granule cell-specific product of the CaM kinase TV gene, Eur J Neurosci, 11, pp 2531-6. 

Fig. 11.1 Activation of MAPK pathway by Angll and ET-1 in VSMC. Stimulation of Angll and ET-1 receptors through Gq/n activation enhances the activity of PLCp. Activated PLC 3 converts PIP2 to IP3 and diacylglycerol (DAG). IP3 elevates the concentration of intracellular calcium and DAG activates PKC. PKC and/or Ca2+/calmodulin (CaM)-dependent protein kinases (CaMK) activate nonreceptor (NR) and/or receptor (R) protein tyrosine kinases. Activation of these components signals the stimulation of Ras/Raf/MEK/ERKl/2 and p70 s6k. ERK1/2 and p70 s6k are translocated to nucleus and regulate nuclear events by activating transcription factors through phosphorylation.

If beta cells are incubated in media containing 2 mM glucose and then treated with forskolin and/or tolbutamide, there is a small transient increase in insulin secretion. The subsequent addition of CCK8S leads to a very marked first phase of insulin secretion, but causes no sustained increase or second phase of insulin secretion. These results mean that an increase in cAMP alters the Ca2+ sensitivity of the response elements underlying the first phase of secretion. These elements, presumed to be Ca2+-calmodulin-dependent processes including CaM-dependent protein kinases, become more sensitive to activation by Ca2+ either because cAMP acts to enhance the sensitivity of CaM-dependent kinases to Ca2+, or because cAMP inhibits, by an unknown mechanism, the activity of phosphoprotein phosphatases. 

The conclusions from this analysis are (a) that Ca2+ influx rate (and hence Ca2+ cycling) is the prime determinant of the magnitude of a sustained cellular response in cells whose response is controlled via the Ca2+ messenger system and (b) this is true whether the particular response is mediated via the synarchic interaction of Ca2+ and cAMP, or by the coordinate, Ca2+-dependent regulation of CaM-dependent protein kinases and protein kinase C [31]. 

FIGURE 21-6 Schematic illustration of the overall structure and regulatory sites of eleven different phosphodiesterase subtypes. The catalytic domain of the phosphodiesterases are relatively conserved, and the preferred substrate(s) for each type is shown. The regulatory domains are more variable and contain the sites for binding of Ca2+/calmodulin (CaM) and cGMP, as well as GAF and PAS domains. The regulatory domains also contain sites of phosphorylation by cAMP-dependent protein kinase (PKA). 

PDE1 is phosphorylated by Ca27calmodulin-dependent protein kinase II (CaM-kinase II), which results in decreased affinity of this enzyme for Ca2+/calmodulin and an increase in the concentration of Ca2+ needed for its activation. PDE1 is also phosphorylated by protein kinase A, which likewise decreases its binding to Ca27calmodulin. 

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