Camps, Francis

Of the protein kinases, protein kinase A is the best investigated and characterized (review Francis and Corbin, 1994). The functions of protein kinase A are diverse. Protein kinase A is involved in the regulation of metabolism of glycogen, lipids and sugars. Substrates of protein kinase A may be other protein kinases, as well as enzymes of intermediary metabolism. Protein kinase A is also involved in cAMP-stimulated transcription of genes that have a cAMP-responsive element in their control region (review Montminy, 1997). An increase in cAMP concentration leads to activation of protein kinase A which phosphorylates the transcription factor CREB at Ser 133. CREB only binds to the transcriptional coactivator CBP in the phosphorylated state and stimulates transcription (see Chapter 1.4.4.2). 

Zhao Z, Francis CE, Ravid K (1997) An A3-subtype adenosine receptor is highly expressed in rat vascular smooth muscle cells its role in attenuating adenosine-induced increase in camp. Microvasc Res 54(3) 243-252... 

Zhao Z, Makaritsis K, Francis CE, Gavras H, Ravid K (2000) A role for the A3 adenosine receptor in determining tissue levels of cAMP and blood pressure studies in knock-out mice. Biochim Biophys Acta 1500(3) 280-290... 

Francis SH, Corbin JD (1999) Cyclic nucleotide-dependent protein kinases intracellular receptors for cAMP and cGMP action. Crit Rev Clin Lab Sci 36 275-328... 

Francies E. Camps, Medical and Scientific Investigations in the Christie Case, Medical Publications Ltd., London 1953 Louis Cavare, Le droit internationalpublique positif, v. 1, Pichon et Durand-Auzias, Paris 1951 Stephen Challen, RichardKorherr and his Reports, Cromwell Press, London 1993... 

Reed RB, Satdba-g M, Jahnsen T, Lohmann SM, Francis SH, Corbin JD. Fast and slow cyclic nucleotide-dissodation rites in cAMP-dependent protein kinase are transposed in type Ib cGMP-dependent protein kinase. JBiol Chem 19% 271 17570-17575. 

Smith, J. A., Francis, S-, VVhlsh, K Kumar, S., and Corbin, J. (1996). Autophosphorylation of type Ib cGMP-dependent protein Idnase increases basal catalytic activity and enhances allosteric activation by cGMP or cAMP / Bio . Chem. 271,20756-20762. 

McPhee SW, Janson CG, Li C, Samulski RJ, Camp AS, Francis J, Shera D, Lioutermann L, Feely M, Ereese A, Leone P. Immune responses to AAV in a phase I study for Canavan disease. J Gene Med 2006 8 577-588. 

Degradation ofcAMPby cAMP phosphodiesterases is also an importantpointofattack for control of the cAMP level. More than ten different isoforms of phosphodiesterase are known, which vary in their cyclic nucleotide specificity and in their regulation. The phosphodiesterases are subject toavariety of regulatory influences, includingregulation by Ca2+/calmodulin and by protein phosphorylation (review Francis et ah, 2001). 

Zoraghi R, Corbin JD, Francis SH (2006) Phosphodiesterase-5 Gln817 is critical for cGMP, vardenafil, or sildenafil affinity its orientation impacts cGMP but not cAMP affinity. J Biol Chem 281 5553-5558... 

Vasta V (2006) cAMP-phosphodiesterase 8 family. In Beavo JA, Francis SH, Houslay MD (eds) Cyclic nucleotide phosphodiesterases in health and disease. CRC, Boca Raton, FL... 

Jiang, H., Colbran, J. L., Francis, S. H., et al. (1992). Direct evidence for cross-activation of cGMP-dependent protein kinase by cAMP in pig coronary arteries. J. Biol. Chem. 267, 1015-1019. 

Dehumanised and brutally objectified into a pitiful animalistic state, Lear s re-envisioning of himself evokes associations of the victims of the Nazi concentration camps. There are also evocations of the crucifix-creatures in some of the immediate post-war paintings of Francis Bacon and Graham Sutherland. 

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