The Direct Interaction of Phospholipase C-γ1 with Phospholipase D2 Is Important for Epidermal Growth Factor Signaling

Jang, Il Ho; Lee, Sukmook; Park, Jong Bae; Kim, Jong Hyun; Lee, Chang Sup; Hur, Eun Mi; Kim, Il Shin; Kim, Kyong‐Tai; Yagisawa, Hitoshi; Suh, Pann‐Ghill; Ryu, Sung Ho

doi:10.1074/jbc.m208438200

Cited by 51 publications

(40 citation statements)

References 70 publications

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“…Molecular analysis of the interaction between endogenous Grb2 and PLD2 mutants revealed that (Xu et al, 2001), whereas residue Y 179 is conserved only in the PX domain of mammalian PLDs. The N-terminal region of PLD2, containing the PX (a.a. and domains, is the most representative region involved in PLD2 protein-protein interactions (Park et al, 2000;Kim et al, 2002;Ahn et al, 2003;Jang et al, 2003). The relevance of the PX domain is illustrated by the fact that its deletion from PLD2 produces a catalytically inactive enzyme in vitro (Sung et al, 1999;Park et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

The elucidation of novel SH2 binding sites on PLD2

et al. 2006

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Section: Discussionmentioning

confidence: 99%

The elucidation of novel SH2 binding sites on PLD2

et al. 2006

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“…In contrast, the extra five residues in γ and δ isoforms (splice site 2) occur within a region that is variable in other PX domains. This insertion aligns within the "PXXP" motif of p47 phox and PLD1, which is exposed and can engage in either intramolecular or intermolecular protein-protein interactions [34,38]. Several other proteins contain PX domains that lack this proline-rich motif entirely [27].…”

Section: Alternative Splicing Of Noxo1 and Its Effects On Px Domain Smentioning

confidence: 99%

Subcellular localization and function of alternatively spliced Noxo1 isoforms

Ueyama

Lekstrom

Tsujibe

et al. 2007

Free Radical Biology and Medicine

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Nox organizer 1 (Noxo1), a p47 phox homolog, is produced as four isoforms with unique N-terminal PX domains derived by alternative mRNA splicing. We compared the subcellular distribution of these isoforms or their isolated PX domains produced as GFP fusion proteins, as well as their ability to support Nox1 activity in several transfected models. Noxo1α, β, γ, and δ show different subcellular localization patterns, determined by their PX domains. In HEK293 cells, Noxo1β exhibits prominent plasma membrane binding, Noxo1γ shows plasma membrane and nuclear associations, Noxo1α and δ localize primarily on intracellular vesicles or cytoplasmic aggregates, but not the plasma membrane. Nox1 activity correlates with Noxo1 plasma membrane binding in HEK293 cells, since Noxo1β supports the highest activity and Noxo1γ and Noxo1α support moderate or low activities, respectively. In COS-7 cells, where Noxo1α localizes on the plasma membrane, the activities supported by the three isoforms (α, β, and γ) do not differ significantly. The PX domains of β and γ bind the same phospholipids, including phosphatidic acid. These results indicate the variant PX domains are unique determinants of Noxo1 localization and Nox1 function. Finally, the overexpressed Noxo1 isoforms do not affect p22 phox localization, although Nox1 is needed to transport p22 phox to the plasma membrane.

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“…PX domains are found in a range of proteins associated with membranes such as PLD, sorting nexins and yeast Vam7p, and contain a proline-rich motif, which enables them to recognize the Src homology 3 (SH3) domain (Jang et al, 2003;Kay et al, 2000;Ponting, 1996). Moreover, recent studies have shown that, specific interactions between PX domains and phosphoinositides play a crucial role in the localization and enzymatic regulation of PX-domaincontaining proteins, and have identified the PX domain as a phosphoinositide-binding module involved in cellular signal transduction Cheever et al, 2001;Ellson et al, 2001;Kanai et al, 2001;Xu et al, 2001;Zhan et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Phosphatidylinositol (3,4,5)-trisphosphate specifically interacts with the phox homology domain of phospholipase D1 and stimulates its activity

Lee

Kim

Jang

et al. 2005

Journal of Cell Science

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Phospholipase D (PLD), which catalyzes the hydrolysis of phosphatidylcholine to phosphatidic acid and choline, plays key roles in cellular signal transduction by mediating extracellular stimuli including hormones, growth factors, neurotransmitters, cytokines and extracellular matrix molecules. The molecular mechanisms by which domains regulate the activity of PLD - especially the phox homology (PX) domain - have not been fully elucidated. In this study, we have examined the properties of the PX domains of PLD1 and PLD2 in terms of phosphoinositide binding and PLD activity regulation. Interestingly, the PX domain of PLD1, but not that of PLD2, was found to specifically interact with phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3). We found that mutation of the conserved arginine at position 179 of the PLD1 PX domain to lysine or to alanine (R179A or R179K, respectively) disrupts PtdIns(3,4,5)P3 binding. In NIH-3T3 cells, the EGFP-PLD1 PX wild-type domain, but not the two mutants, localized to the plasma membrane after 5-minute treatment with platelet-derived growth factor (PDGF). The enzymatic activity of PLD1 was stimulated by adding PtdIns(3,4,5)P3 in vitro. Treatment with PDGF resulted in the significant increase of PLD1 activity and phosphorylation of the downstream extracellular signal-regulated kinases (ERKs), which was blocked by pre-treatment of HEK 293 cells with phosphoinositide 3-kinase (PI3K) inhibitor after the endogenous PLD2 had been depleted by siRNA specific for PLD2. Nevertheless, both PLD1 mutants (which cannot interact with PtdIns(3,4,5)P3) did not respond to treatment with PDGF. Moreover, PLD1 was activated in HepG2 cells stably expressing the Y40/51 mutant of PDGF receptor that is required for the binding with PI3K. Our results suggest that the PLD1 PX domain enables PLD1 to mediate signal transduction via ERK1/2 by providing a direct binding site for PtdIns(3,4,5)P3 and by activating PLD1.

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The Direct Interaction of Phospholipase C-γ1 with Phospholipase D2 Is Important for Epidermal Growth Factor Signaling

Cited by 51 publications

References 70 publications

The elucidation of novel SH2 binding sites on PLD2

The elucidation of novel SH2 binding sites on PLD2

Subcellular localization and function of alternatively spliced Noxo1 isoforms

Phosphatidylinositol (3,4,5)-trisphosphate specifically interacts with the phox homology domain of phospholipase D1 and stimulates its activity

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