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rdf:type |
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lifeskim:mentions |
umls-concept:C0010531,
umls-concept:C0017262,
umls-concept:C0026882,
umls-concept:C0027651,
umls-concept:C0332281,
umls-concept:C0580822,
umls-concept:C1171362,
umls-concept:C1280500,
umls-concept:C1418907,
umls-concept:C1515670,
umls-concept:C1547300,
umls-concept:C1548760,
umls-concept:C1550594
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pubmed:issue |
9
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pubmed:dateCreated |
2008-5-2
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pubmed:abstractText |
Most PRKAR1A tumorigenic mutations lead to nonsense mRNA that is decayed; tumor formation has been associated with an increase in type II protein kinase A (PKA) subunits. The IVS6+1G>T PRKAR1A mutation leads to a protein lacking exon 6 sequences [R1 alpha Delta 184-236 (R1 alpha Delta 6)]. We compared in vitro R1 alpha Delta 6 with wild-type (wt) R1 alpha. We assessed PKA activity and subunit expression, phosphorylation of target molecules, and properties of wt-R1 alpha and mutant (mt) R1 alpha; we observed by confocal microscopy R1 alpha tagged with green fluorescent protein and its interactions with Cerulean-tagged catalytic subunit (C alpha). Introduction of the R1 alpha Delta 6 led to aberrant cellular morphology and higher PKA activity but no increase in type II PKA subunits. There was diffuse, cytoplasmic localization of R1 alpha protein in wt-R1 alpha- and R1 alpha Delta 6-transfected cells but the former also exhibited discrete aggregates of R1 alpha that bound C alpha; these were absent in R1 alpha Delta 6-transfected cells and did not bind C alpha at baseline or in response to cyclic AMP. Other changes induced by R1 alpha Delta 6 included decreased nuclear C alpha. We conclude that R1 alpha Delta 6 leads to increased PKA activity through the mt-R1 alpha decreased binding to C alpha and does not involve changes in other PKA subunits, suggesting that a switch to type II PKA activity is not necessary for increased kinase activity or tumorigenesis.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-10480911,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-10620803,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-10625697,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-10973256,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-11115848,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-11350809,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-12004056,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-12119269,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-12119272,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-12203783,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-12210127,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-12242045,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-12424709,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-12692076,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-12812976,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-14500362,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-15264254,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-15274925,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-15331577,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-15591278,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-15604237,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-15692043,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-15930266,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-16214430,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-16407073,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-16524697,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-16937372,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-16963469,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-17079485,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-17182741,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-17204847,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-17884635,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-17889648,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-18223213,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-2557506,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-7756252,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-8298196,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-8388994,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-8822496,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-9344252,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18451138-9434753
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1538-7445
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pubmed:author |
pubmed-author:BertheratJérômeJ,
pubmed-author:BossisIoannisI,
pubmed-author:CazabatLaureL,
pubmed-author:FumeyGlawdysG,
pubmed-author:GroussinLionelL,
pubmed-author:HorvathAneliaA,
pubmed-author:MavrakisManosM,
pubmed-author:MeoliEliseE,
pubmed-author:MuchowMichaelM,
pubmed-author:NesterovaMariaM,
pubmed-author:PatronasYiannaY,
pubmed-author:PerlemoineKarineK,
pubmed-author:Robinson-WhiteAudreyA,
pubmed-author:ShiferawMiriam LML,
pubmed-author:StergiopoulosSotirisS,
pubmed-author:StratakisConstantine ACA,
pubmed-author:WeinbergFrankF
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
68
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3133-41
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pubmed:dateRevised |
2011-8-1
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pubmed:meshHeading |
|
