Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1992-10-7
pubmed:abstractText
Previous studies have demonstrated that the Dictyostelium G alpha subunit G alpha 2 is essential for the cAMP-activation of adenylyl cyclase and guanylyl cyclase and that g alpha 2 null mutants do not aggregate. In this manuscript, we extend the analysis of the function of G alpha 2 in regulating downstream effectors by examining the in vivo developmental and physiological phenotypes of both wild-type and g alpha 2 null cells carrying a series of mutant G alpha 2 subunits expressed from the cloned G alpha 2 promoter. Our results show that wild-type cells expressing G alpha 2 subunits carrying mutations G40V and Q208L in the highly conserved GAGESG (residues 38-43) and GGQRS (residues 206-210) domains, which are expected to reduce the intrinsic GTPase activity, are blocked in multicellular development. Analysis of down-stream effector pathways essential for mediating aggregation indicates that cAMP-mediated activation of guanylyl cyclase and phosphatidylinositol-phospholipase C (PI-PLC) is almost completely inhibited and that there is a substantial reduction of cAMP-mediated activation of adenylyl cyclase. Moreover, neither mutant G alpha 2 subunit can complement g alpha 2 null mutants. Expression of G alpha 2(G43V) and G alpha 2(G207V) have little or no effect on the effector pathways and can partially complement g alpha 2 null cells. Our results suggest a model in which the dominant negative phenotypes resulting from the expression of G alpha 2(G40V) and G alpha 2(Q208L) are due to a constitutive adaptation of the effectors through a G alpha 2-mediated pathway. Analysis of PI-PLC in g alpha 2 null mutants and in cell lines expressing mutant G alpha 2 proteins also strongly suggests that G alpha 2 is the G alpha subunit that directly activates PI-PLC during aggregation. Moreover, overexpression of wild-type G alpha 2 results in the ability to precociously activate guanylyl cyclase by cAMP in vegetative cells, suggesting that G alpha 2 may be rate limiting in the developmental regulation of guanylyl cyclase activation. In agreement with previous results, the activation of adenylyl cyclase, while requiring G alpha 2 function in vivo, does not appear to be directly carried out by the G alpha 2 subunit. Our data are consistent with adenylyl cyclase being directly activated by either another G alpha subunit or by beta gamma subunits released on activation of the G protein containing G alpha 2.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-1312225, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-1668191, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-1668648, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-1670774, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-1692327, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-1730644, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-1849108, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-1898771, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-1902986, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-1930158, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-1962211, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-1968413, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-1986000, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-2022671, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-2110382, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-2122258, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-2163344, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-2192261, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-2500658, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-2538821, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-2539262, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-2545115, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-2546676, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-2548581, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-2549064, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-2549065, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-2549426, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-2550214, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-2556709, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-2672337, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-2821026, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-2821029, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-2843545, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-2843553, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-2844774, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-2846388, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-2846597, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-2854023, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-2890646, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-2893972, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-3031475, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-3036630, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-3037274, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-3039908, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-3047871, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-3113327, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-3139030, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-3244804, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-3362676, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-3405751, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-4075402, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-6249827, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-6304109, http://linkedlifedata.com/resource/pubmed/commentcorrection/1355376-6309779
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1059-1524
pubmed:author
pubmed:issnType
Print
pubmed:volume
3
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
735-47
pubmed:dateRevised
2010-9-7
pubmed:meshHeading
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