Protein kinase tissue distribution

AdCy Effect of Gaj Effect of gpy Effects of Ca2+and/or calmodulin Effects of protein kinases Tissue distribution Physiological functions... 

Protein kinase B, or Akt, was discovered as the product of an oncogene of the acutely transforming retrovirus AKT8, causing T-cell lymphomas in mice. It encodes a fusion product of a cellular serine/threonine protein kinase and the viral structural protein Gag. This kinase is similar to both protein kinase Ce (PKCe 73% identity to the catalytic domain) and protein kinase A (PKA 68%). It differs from other protein kinases in that it contains a pleckstrin homology (PH) domain, which allows it to bind to polyphosphoinositide head groups (and also to G-protein fly subunits). To date, three subtypes have been identified a, (3, and y, all of which show a broad tissue distribution. It... 

Protein kinases differ in their cellular and subcellular distribution, substrate specificity and regulation. These properties determine the functional roles played by the very large number of protein kinases that have been found in mammalian tissues, most of which are known to be expressed in neurons [3]. The major classes of protein serine-threonine kinase in the brain, listed in Table 23-1, are covered in this chapter. The major classes of protein tyrosine kinases in the brain are discussed in Chapter 24. 

Inositol trisphosphate, a water-soluble compound, diffuses from the plasma membrane to the endoplasmic reticulum, where it binds to specific IP3 receptors and causes Ca2+ channels within the ER to open. Sequestered Ca2+ is thus released into the cytosol (step (5)), and the cytosolic [Ca2+] rises sharply to about 10 6 m. One effect of elevated [Ca2+] is the activation of protein kinase C (PKC). Diacylglycerol cooperates with Ca2+ in activating PKC, thus also acting as a second messenger (step (6)). PKC phosphorylates Ser or Thr residues of specific target proteins, changing their catalytic activities (step (7)). There are a number of isozymes of PKC, each with a characteristic tissue distribution, target protein specificity, and role. 

In the body, enzymes are compartmentalized and function under highly restricted conditions. Some enzymes (e.g., proteinases) are not substrate-specific. When present in active form in an inappropriate part of the body, they act indiscriminately and cause considerable damage to the tissue. Inhibitors inactivate these enzymes at sites where their action is not desired. Proteinase inhibitors, which are themselves proteins, are widely distributed in intracellular and extracellular fluids. Protein inhibitors of enzymes other than proteinases are relatively rare. Such inhibitors are available for a-amylases, deoxyribonuclease I, phospholipase A, and protein kinases. 

Wetsel WC, Khan WA, Merchenthaler 1, Rivera H, Halpern AE, Phung HM, Negro-Vilar A, Hannun YA (1992) Tissue and cellular distribution of the extended family of protein kinase C isoenzymes. J. Cell Biol, 117, 121-133. 

The cyclic AMP-dependent protein kinases are widely distributed in animal tissues but have not yet been found in higher plants (89). They are made up of regulatory (R) and catalytic (C) subunits. Cyclic AMP binds to the regulatory subunit causing dissociation of the RC complex to form the active subunit (C) (Equation 11) ... 

Protein kinases C (PKC) catalyze protein phosphorylations, a pivotal step in signal generation and transduction in cells. PKC s are widely distributed in tissue and organs (73). They constitute a family of enzymes with at least seven isoforms. Nearly 100 PKC s are known and a large number of receptors, growth factors and products of oncogenes are PKC s. In connection with the discussion of nAChR s it may be noted that PKC is involved in the regulation of this ion channel (74). 

Walter, U. (1988). Distribution of cyclic GMP-dependent protein kinase in various rat tissues and cell lines determined by a sensitive and specific radioimmunossay. Eur. J. Biochem. 118, 339-346. 

Fox, G.M. Holst, P.L. Chute, H.T. Lindberg, R.A. Janssen, A.M. Basu, R. Welcher, A.A. cDNA cloning and tissue distribution of five human EPH-like receptor protein-tyrosine kinases. Oncogene, 10, 897-905 (1995)... 

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