Ca-CaM-dependent protein kinase

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. 

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

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. 

In contrast, little is known about the regulation of the Cav3 family of channels. However, in the case of Ca /CaM regulation it seems to depend on the activity of the Ca VCaM-dependent protein kinase n. Thus, activation of this kinase in cells expressing recombinant Cav3.2 channels increases current amphtude at negative test potentials as the result of Seri 198 phosphorylation within the linker connecting domains II and III in the tti subunit [135,136]. 

C-Kinase protein kinase C, A-kinase cAMP-dependent protein kinase, CaM-kinase Ca +/calmodulin-dependent protein kinase. 

Regulation of glycogen synthase by multisite phosphorylation. The location of phosphorylation sites ( ) and the protein kinases that phosphorylate at these sites (boxes) are shown. Phosphorylations occur only at N- and C-terminal regions of the enzymes, as indicated by CB-N and CB-C, respectively. The single-letter abbreviations for amino acids are used (see Chapter 2). cAMP-PK = cyclic AMP-dependent protein kinase CAM-MPK = Ca +/calmodulin-dependent multiprotein kinase PhK = phosphorylase kinase GSK = glycogen synthase kinase CK = casein kinase NIO-PK = A novel protein kinase. [Reproduced with permission from P. Cohen, Protein phosphorylation and hormone action. Proc. R. Soc. Lonrf. (Biol.) 234, 115(1988).]... 

Depolarization of the nerve terminal activates tyrosine hydroxylase. Depolarization also activates a number of protein kinases (including protein kinase C, protein kinase A [the cAMP-dependent protein kinase] and CAM kinases [Ca -calmodulin-dependent kinases]) that phosphorylate tyrosine hydroxylase. These activation steps result in an enzyme that binds BH4 more tightly, making it less sensitive to end-product inhibition. 

Describe the structure of calmodulin and its biochemical function. Relate calmodulin to the calmodulin-dependent protein kinase (CaM Kinase) and the Ca -ATP ion pump. Note the value of calcium ionophores, calcium buffers, and fluorescent indicators in studying the functions of Ca " in cells. 

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