Dependence and protein kinase

Haring, R. et al., 1998. Mitogen-activated protein kinase-dependent and protein kinase C-dependent pathways link the m, muscarinic receptor to (3-amyloid precursor protein secretion. J. Neurochem. 7, 2094-2103. 

Heterologous desensitization is a form of desensitization which does not require agonist binding of the receptor. Second messenger dependent kinases such as protein kinase A (PKA) and protein kinase C (PKC) are involved in this form of receptor desensitization. Heterologous desensitization simply depends on the overall kinase activity which is regulated by many different stimuli. 

Mestek A, Hurley JH, Bye LS et al. The human k opioid receptor modulation of functional desensitization by calcium/cal-modulin-dependent protein kinase and protein kinase C. J Neurosci 1995 15 2396-2406. 

Chen Y, Yu L. Differential regulation by cAM P-dependent protein kinase and protein kinase C of the k opioid receptor coupling to a G protein-activated K+ channel. J Biol Chem 1994 269 7839-7842. 

Alreja M, Aghajanian G. Pacemaker activity of locus coeruleus neurons whole-cell recordings in brain slices show dependence on cAMP and protein kinase A. Brain Res 1991 556 339—343. Shiekhattar R, Aston-Jones G. Modulation of opiate responses in brain noradrenergic neurons by cAMP cascade changes with chronic morphine. Neuroscience 1993 57 879-885. 

In this laboratory, we also include the metal ion chelators EDTA (ethylene diamine tetraacetic acid binds, e.g., Mg2 1 -ions) and EGTA (ethylene glycol-bis(2-aminoethyl)-Al,iV,iV/,iV/,-tetraacetic acid binds, e.g., Ca2+-ions) in our lysis buffers. These agents help prevent phosphatase action (by the metal ion-dependent phosphatase PP2C, which is not inhibited by microcystin-LR), metal (Ca2+) dependent proteinases, and protein kinases, which require divalent cations such as Mg2 1 (and, in some cases, also Ca2+). We also use a mix of proteinase inhibitors that inhibit a broad range of proteolytic enzymes, including serine and cysteine proteinases. 

Cox, D. A. and Cohen, M. L. 5-HT2B receptor signaling in the rat stomach fundus dependence on calcium influx, calcium release and protein kinase C. Behav. Brain Res. 73 289-292,1996. 

Several key questions remain with regard to the regulation of tyrosine hydroxylase by phosphorylation. What is the precise effect of the phosphorylation of each of these serine residues on the catalytic activity of the enzyme How does the phosphorylation of multiple residues affect enzyme activity Does the phosphorylation of one residue affect the ability of the others to be phosphorylated Tyrosine hydroxylase provides a striking example as to how multiple intracellular messengers and protein kinases converge functionally through the phosphorylation of a single substrate protein. Phosphorylation of tyrosine hydroxylase by cAMP-dependent and Ca2+-dependent protein kinases and by MAPK cascades... 

It is known that protein kinase C can phosphorylate a number of key oxidase components, such as the two cytochrome b subunits and the 47-kDa cytoplasmic factor. This process is prevented by protein kinase C inhibitors such as staurosporine (although it is now recognised that this inhibitor is not specific for protein kinase C), which also inhibits the respiratory burst activated by agonists such as PMA. However, when cells are stimulated by fMet-Leu-Phe, translocation of pAl-phox to the plasma membrane can occur even if protein kinase C activity is blocked - that is, phosphorylation is not essential for the translocation of this component in response to stimulation by this agonist. Similarly, the kinetics of phosphorylation of the cytochrome subunits do not follow the kinetics of oxidase activation, and protein kinase C inhibitors have no effect on oxidase activity elicited by some agonists -for example, on the initiation of the respiratory burst elicited by agonists such as fMet-Leu-Phe (Fig. 6.14). Furthermore, the kinetics of DAG accumulation do not always follow those of oxidase activity. Hence, whilst protein kinase C is undoubtedly involved in oxidase activation by some agonists, oxidase function is not totally dependent upon the activity of this kinase. 

Second-messenger-dependent kinases, such as cAMP-dependent protein kinase A (PKA) and protein kinase C (PKC), are most often implicated in heterologous desensitization (123,129) however, the systems involved may vary between cell types (130). These protein kinases are associated with GPCR desensitization that... 

The structural integrity of the cell membrane is irreversibly damaged by the process of membrane lipid peroxidation. The damaged membrane becomes leaky and extracellular calcium enters the cell. This in turn activates calcium-dependent phospholipases and protein kinases, subsequently leading to fatty acid cleavage and other biochemical alterations within the cell. Ultimately this leads to damage or death of the cell. 

The TAFs are components of TFIID (see table 1.1) and are required for a regulated transcription (review Verriijzer and Tijan 1996, Bmley and Roeder, 1996 ). Thus, the stimulation of transcription by the transcriptional activators Spl and NTF-1 depends upon the presence of specific TAFs in the TFllD complex. The TAFs mediate interactions between the transcriptional activators and the TFllD complex in many cases direct protein-protein interactions could be demonstrated between the activators and TAFs. Some of the TAFs possess additional enzymatic activities which allow them to participate in the regulation of transcription. By this token, the histone acetylase and protein kinase activity of TAFn250 is ascribed a regulatory function in the remodeling of chromatin and in the control of the activity of the basal transcription factors. 

With its multiple second messengers and protein kinases, the phosphoinositide signaling pathway is much more complex than the cAMP pathway. For example, different cell types may contain one or more specialized calcium- and calmodulin-dependent kinases with limited substrate specificity (eg, myosin light-chain kinase) in addition to a general calcium- and calmodulin-... 

Ikebe, M. Reardon, S. Scott-Woo, G.C. Zhou, Z. Koda, Y. Purification and characterization of calmodulin-dependent multifunctional protein kinase from smooth muscle isolation of caldesmon kinase. Biochemistry, 29, 11242-11248 (1990)... 

Communi, D. Dewaste, V. Erneux, C. Calcium-calmodulin-dependent protein kinase II and protein kinase C-mediated phosphorylation and activation of D-myo-inositol 1,4, 5-trisphosphate 3-kinase B in astrocytes. J. Biol. Chem., 274, 14734-14742 (1999)... 

Leonard, A. S. and Hell, J. W. Cyclic AMP-dependent protein kinase and protein kinase C phosphorylate N-methyl-D-aspartate receptors at different sites, J. Biol. Chem. 1997, 272, 12107-12115. 

Moriguchi S., Han F., Nakagawasai O., Tadano T., and Fukunaga K. (2006). Decreased calcium/calmodulin-dependent protein kinase II and protein kinase C activities mediate impairment of hippocampal long-term potentiation in the olfactory bulbectomized mice. J. Neurochem. 97 22-29. 

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