Activated Gα Subunits Can Inhibit Multiple Signal Transduction Pathways during Dictyostelium Development

Srinivasan, Jaishree; Gundersen, Robert E.; Hadwiger, Jeffrey A.

doi:10.1006/dbio.1999.9474

Cited by 16 publications

(14 citation statements)

References 42 publications

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“…Folate stimulation does not involve a pulsatile signal but the response is likely to require an adaptation process, typically found in other eukaryotic chemotactic responses [35]. Stimulation of Dictyostelium with either cAMP or folate results in a rapid accumulation of cGMP that peaks within 15 s and a slightly slower accumulation of cAMP that peaks about 2 min after stimulation [36–38]. The accumulation of cAMP is likely to be regulated in part by the down regulation of the cAMP-specific phosphodiesterase RegA by active ERK2 and the cessation of cAMP accumulation could possibly be attributed to the loss of ERK2 activity and a gain of RegA activity [19].…”

Section: Discussionmentioning

confidence: 99%

The Dictyostelium MAPK ERK1 is phosphorylated in a secondary response to early developmental signaling

Schwebs¹,

Hadwiger²

2015

Cellular Signalling

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Previous reports have suggested that the two mitogen-activated protein kinases (MAPKs) in Dictyostelium discoideum, ERK1 and ERK2, can be directly activated in response to external cAMP even though these MAPKs play different roles in the developmental life cycle. To better characterize MAPK regulation, the levels of phosphorylated MAPKs were analyzed in response to external signals. Only ERK2 was rapidly phosphorylated in response to the chemoattractants, cAMP and folate. In contrast, the phosphorylation of ERK1 occurred as a secondary or indirect response to these stimuli and this phosphorylation was enhanced by cell-cell interactions, suggesting that other external signals can activate ERK1. The phosphorylation of ERK1 or ERK2 did not require the function of the other MAPK in these responses. Folate stimulation of a chimeric population of erk1− and gα4− cells revealed that the phosphorylation of ERK1 could be mediated through an intercellular signal other than folate. Loss of ERK1 function suppressed the developmental delay and the deficiency in anterior cell localization associated with gα5− mutants suggesting that ERK1 function can be down regulated through Gα5 subunit-mediated signaling. However, no major changes in the phosphorylation of ERK1 were observed in gα5− cells suggesting that the Gα5 subunit signaling pathway does not regulate the phosphorylation of ERK1. These findings suggest that the activation of ERK1 occurs as a secondary response to chemoattractants and that other cell-cell signaling mechanisms contribute to this activation. Gα5 subunit signaling can down regulate ERK1 function to promote prestalk cell development but not through major changes to the level of phosphorylated ERK1.

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Section: Discussionmentioning

confidence: 99%

The Dictyostelium MAPK ERK1 is phosphorylated in a secondary response to early developmental signaling

Schwebs¹,

Hadwiger²

2015

Cellular Signalling

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“…Expression of the Ga5* subunit in ga5 cells resulted in a greater delay in aggregate formation than the delay observed for ga5 cells with no expression vectors. This phenotype is probably due to an inhibition of cAMP chemotaxis previously observed for cells expressing constitutively active Ga5*, Ga4* or Ga2* subunits (Srinivasan et al, 1999). The expression of the Ga5 d2, * subunit did not delay the formation of aggregates by ga5 cells, suggesting that the altered D-motif reduces the aggregation delay associated with the Ga5* subunit.…”

Section: Ga5 Subunit Amino-terminal D-motif Is Important For Early Timentioning

confidence: 59%

“…The Dictyostelium Ga5 subunit functions in a signalling pathway that inhibits folate chemotaxis, promotes a small aggregate size and accelerates tip formation and gene expression during development (Hadwiger et al, 1996;Natarajan et al, 2000;Srinivasan et al, 1999). The activator and receptor for this pathway remain to be determined but a recent study of chimeric Ga subunits suggests that the functional specificity of the Ga5 subunit is not limited to the specificity of receptor coupling but requires interactions with other signalling components (Hadwiger, 2007).…”

Section: Introductionmentioning

confidence: 99%

Gα5 subunit-mediated signalling requires a D-motif and the MAPK ERK1 in Dictyostelium

2010

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The Dictyostelium Ga5 subunit has been shown to reduce cell viability, inhibit folate chemotaxis and accelerate tip morphogenesis and gene expression during multicellular development. Alteration of the D-motif (mitogen-activated protein kinase docking site) at the amino terminus of the Ga5 subunit or the loss of extracellular signal-regulated kinase (ERK)1 diminished the lethality associated with the overexpression or constitutive activation of the Ga5 subunit. The aminoterminal D-motif of the Ga5 subunit was also found to be necessary for the reduced cell size, small aggregate formation and precocious developmental gene expression associated with Ga5 subunit overexpression. This D-motif also contributed to the aggregation delay in cells expressing a constitutively active Ga5 subunit, but the D-motif was not necessary for the inhibition of folate chemotaxis. These results suggest that the amino-terminal D-motif is required for some but not all phenotypes associated with elevated Ga5 subunit functions during growth and development and that ERK1 can function in Ga5 subunit-mediated signal transduction.

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“…At least nine G␣ subunits have been described in Dictyostelium (45,46), but only two of them, G␣2 and G␣4, have been implicated in the activation of AC and GC activity in vivo after stimulation of cells with cAMP and folic acid, respectively (18,19,(21)(22)(23)(24). The results shown in Table I indicate that AC activity of DdGCA kqd in lysates from g␣2 Ϫ or g␣4 Ϫ cells are still stimulated by GTP␥S.…”

Section: Regulation Of Ddgca Activity By Gtp␥s-mentioning

confidence: 99%

GTPγS Regulation of a 12-Transmembrane Guanylyl Cyclase Is Retained after Mutation to an Adenylyl Cyclase

Roelofs¹,

Loovers²,

Haastert

2001

Journal of Biological Chemistry

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DdGCA is a Dictyostelium guanylyl cyclase with a topology typical for mammalian adenylyl cyclases containing 12 transmembrane-spanning regions and two cyclase domain. In Dictyostelium cells heterotrimeric G-proteins are essential for guanylyl cyclase activation by extracellular cAMP. In lysates, guanylyl cyclase activity is strongly stimulated by guanosine 5-3-O-(thio) triphosphate (GTP␥S), which is also a substrate of the enzyme. DdGCA was converted to an adenylyl cyclase by introducing three point mutations. Expression of the obtained DdGCA kqd in adenylyl cyclase-defective cells restored the phenotype of the mutant. GTP␥S stimulated the adenylyl cyclase activity of DdGCA kqd with properties similar to those of the wild-type enzyme (decrease of K m and increase of V max ), demonstrating that GTP␥S stimulation is independent of substrate specificity. Furthermore, GTP␥S activation of DdGCA kqd is retained in several null mutants of G␣ and G␤ proteins, indicating that GTP␥S activation is not mediated by a heterotrimeric G-protein but possibly by a monomeric G-protein.

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Activated Gα Subunits Can Inhibit Multiple Signal Transduction Pathways during Dictyostelium Development

Cited by 16 publications

References 42 publications

The Dictyostelium MAPK ERK1 is phosphorylated in a secondary response to early developmental signaling

The Dictyostelium MAPK ERK1 is phosphorylated in a secondary response to early developmental signaling

Gα5 subunit-mediated signalling requires a D-motif and the MAPK ERK1 in Dictyostelium

GTPγS Regulation of a 12-Transmembrane Guanylyl Cyclase Is Retained after Mutation to an Adenylyl Cyclase

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