Extracellular cAMP-dependent protein kinase (ECPKA) in melanoma

2004 ◽  
Vol 208 (2) ◽  
pp. 187-191 ◽  
Author(s):  
Tsunekazu Kita ◽  
James Goydos ◽  
Elena Reitman ◽  
Roald Ravatn ◽  
Yong Lin ◽  
...  
Development ◽  
1993 ◽  
Vol 119 (1) ◽  
pp. 147-154 ◽  
Author(s):  
N.A. Hopper ◽  
C. Anjard ◽  
C.D. Reymond ◽  
J.G. Williams

Expression of the catalytic (C) subunit of the cAMP-dependent protein kinase (PKA) of Dictyostelium under the control of heterologous, cell-type-specific promoters causes ectopic terminal differentiation. When expressed under the control of a prespore-specific promoter, development is accelerated, to yield highly aberrant fruiting bodies that contain a basal mass of spore cells surrounding a central stalk-like structure. When expressed under the control of a prestalk-specific promoter, development arrests much earlier, at the tight mound stage. Prestalk cells move to the apices of these mounds, apparently normally, but no tip is formed. Most of the prestalk cells remain arrested in their development but there are a few isolated stalk cells scattered within such mounds. We show that extracellular cAMP represses stalk cell-specific gene expression in cells where the kinase is constitutively active, suggesting that inhibition of stalk cell differentiation by cAMP in normal cells (Berks and Kay, 1988) occurs because of an effect of extracellular cAMP on an intracellular signalling pathway independent of PKA. We propose a scheme whereby two separate events, a rise in intracellular cAMP levels and a fall in extracellular cAMP concentration, are required to induce stalk cell differentiation.


1993 ◽  
Vol 340 (1293) ◽  
pp. 305-313 ◽  

During formation of the Dictyostelium slug extracellular cAMP signals direct the differentiation of prespore cells and DIF, a chlorinated hexaphenone, induces the differentiation of prestalk cells. At culmination the slug transforms into a fruiting body, composed of a stalk supporting a ball of spores. A dominant inhibitor of cAMP-dependent protein kinase (PKA) expressed under the control of a prestalk-specific promoter blocks the differentiation of prestalk cells into stalk cells. Analysis of a gene specifically expressed in stalk cells suggests that PKA acts to remove a repressor that prevents the premature induction of stalk cell differentiation by DIF during slug migration. PKA is also necessary for the morphogenetic movement of prestalk cells at culmination. Expression of the PKA inhibitor under control of a prespore-specific promoter blocks the accumulation of prespore mRNA sequences and prevents terminal spore cell differentiation. Thus PKA is essential for progression along both pathways of terminal differentiation but with different mechanisms of action. On the stalk cell pathway it acts to regulate the action of DIF while on the spore cell pathway PKA itself seems to act as the inducer of spore cell maturation. Ammonia, the extracellular signal which regulates the entry into culmination, acts by controlling the intracellular concentration of cAMP and thus exerts its effects via PKA. The fact that PKA is necessary for both prespore and spore gene expression leads us to postulate the existence of a signalling mechanism which converts the progressive rise in cAMP concentration during development into discrete, PKA-regulated gene activation events.


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