CaM-dependent protein kinases

Other studies have demonstrated that the skeletal muscle ai peptide can be phosphorylated in T-tubule membranes by a multifunctional Ca " /calmodulin (CaM)-dependent protein kinase [111], Phosphorylation occurs on the i subunit to an extent of 2 mol phosphate/mol subunit and on the /i subunit to an extent of 0.7-1 mol phosphate/mol channel [108,111]. Phosphorylation catalyzed by the CaM-kinase on the ai subunit is additive to that caused by PKA and occurs on distinct sites [111]. So far, however, we have not observed any functional consequences of phosphorylation of the skeletal muscle Ca channels by the CaM-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. 

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 integrated cellular response of the adrenal glomerulosa cell is determined by the activities of three different protein kinases cAMP-dependent protein kinase, CaM-dependent protein kinases, and C-kinase. A sustained response can be produced by the combined activation either of the cAMP- and CaM-dependent kinases, or of the CaM-dependent kinases and C-kinase. Activation of each type of... 

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]. 

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. 

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