Diverse recognition of non-PxxP peptide ligands by the SH3 domains from p67phox, Grb2 and Pex13p

Kami, Keiichiro

doi:10.1093/emboj/cdf428

Cited by 166 publications

(177 citation statements)

References 42 publications

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“…However, in cells coexpressing p47 phox -IRES2-DsRed2 and GFP-p67 phox (⌬SH3), which disrupts the interaction with p47 phox , no GFP-p67 phox (⌬SH3) translocation to the plasma membrane is seen ( Figure 6A, bottom). This result was further confirmed by complementary experiment using GFP-p67 phox and p47 phox (⌬PR)-IRES2-DsRed2, which also disrupts the interaction with p67 phox (Kami et al, 2002;Massenet et al, 2005). In the cells coexpressing GFP-p67 phox and p47 phox (⌬PR)-IRES2-DsRed2, GFP-p67 phox shows no the translocation to the plasma membrane (data not shown).…”

Section: Targeting Of P67 Phox To Early Endosomes or To The Plasma Mementioning

confidence: 59%

A Regulated Adaptor Function of p40^phox: Distinct p67^phoxMembrane Targeting by p40^phoxand by p47^phox

Ueyama

Tatsuno

Kawasaki

et al. 2007

MBoC

101

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In the phagocytic cell, NADPH oxidase (Nox2) system, cytoplasmic regulators (p47 phox , p67 phox , p40 phox , and Rac) translocate and associate with the membrane-spanning flavocytochrome b 558 , leading to activation of superoxide production. We examined membrane targeting of phox proteins and explored conformational changes in p40 phox that regulate its translocation to membranes upon stimulation. GFP-p40 phox translocates to early endosomes, whereas GFP-p47 phox translocates to the plasma membrane in response to arachidonic acid. In contrast, GFP-p67 phox does not translocate to membranes when expressed alone, but it is dependent on p40 phox and p47 phox for its translocation to early endosomes or the plasma membrane, respectively. Translocation of GFP-p40 phox or GFP-p47 phox to their respective membrane-targeting sites is abolished by mutations in their phox (PX) domains that disrupt their interactions with their cognate phospholipid ligands. Furthermore, GFP-p67 phox translocation to either membrane is abolished by mutations that disrupt its interaction with p40 phox or p47 phox . Finally, we detected a head-to-tail (PX-Phox and Bem1 [PB1] domain) intramolecular interaction within p40 phox in its resting state by deletion mutagenesis, cell localization, and binding experiments, suggesting that its PX domain is inaccessible to interact with phosphatidylinositol 3-phosphate without cell stimulation. Thus, both p40 phox and p47 phox function as diverse p67 phox "carrier proteins" regulated by the unmasking of membrane-targeting domains in distinct mechanisms. INTRODUCTIONIn phagocytic cells, reactive oxygen species (ROS) are produced by NADPH oxidase (Nox2 system). The enzyme is a multiprotein complex assembled from a membrane-spanning flavocytochrome b 558 (composed of gp91 phox [Nox2] and p22 phox ) and four cytoplasmic components (p47 phox , p67 phox , p40 phox , and Rac) (Leto, 1999;Nauseef, 2004;Quinn and Gauss, 2004). In unstimulated phagocytes, the oxidase is dissociated and inactive: the flavocytochrome b 558 is stored on the membranes of intracellular granules (Jesaitis et al., 1990), Rac is maintained in a GDP-bound cytoplasmic complex dimerized with Rho-guanine nucleotide dissociation inhibitor (GDI) , and the other phox proteins associate in a separate ternary cytoplasmic complex (p47 phox -p67 phox -p40 phox ) in a dephosphorylated state (Bolscher et al., 1989;Rotrosen and Leto, 1990;Kuribayashi et al., 2002;Lapouge et al., 2002). During phagocyte activation, intracellular granules containing flavocytochrome b 558 fuse with phagosomes; p47 phox is phosphorylated, thereby inducing conformational changes in p47 phox that promote the interaction of the cytoplasmic complex with the flavocytochrome b 558 ; and Rac dissociates from Rho-GDI and translocates independently to the membrane after exchange of GDP for GTP (Heyworth et al., 1994;Zhao et al., 2003), resulting in generation of superoxide anion by the transfer of electrons from cytoplasmic NADPH to molecular oxygen.Chronic granulomatous disease...

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Section: Targeting Of P67 Phox To Early Endosomes or To The Plasma Mementioning

confidence: 59%

A Regulated Adaptor Function of p40^phox: Distinct p67^phoxMembrane Targeting by p40^phoxand by p47^phox

Ueyama

Tatsuno

Kawasaki

et al. 2007

MBoC

101

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“…It is also known that p47 phox associates with p67 phox via the C-terminal region containing the PRR (17)(18)(19). As shown in Fig.…”

Section: Figmentioning

confidence: 94%

“…1B). In addition to the PRR of p41 nox , its C-terminally flanking region is also similar to that of p47 phox , which plays an important role in binding to p67 phox together with the PRR (19). On the other hand, p41 nox lacks a region that is expected to mask its SH3 domains; the corresponding region of p47 phox (amino acids 286 -340), the AIR, intramolecularly binds to the SH3 domains, and thereby prevents the domains from binding to the target p22 phox (22).…”

Section: Primary Structure and Domain Architecture Of P41 Nox Amentioning

confidence: 99%

“…2, A and B). The most conserved region is the C-terminal SH3 domain, with 52% identity, a domain of p67 phox known to directly bind to the C-terminal PRR of p47 phox (17)(18)(19). It is also known that p67 phox interacts with p40 phox via the Phox and Bem 1 (PB1) domain between the SH3 domains (47).…”

Section: Figmentioning

confidence: 99%

“…In this process, p47 phox translocates to the membrane by itself, whereas p67 phox is recruited via p47 phox (15,16); they constitutively associate via a tail-to-tail interaction (17)(18)(19). p47 phox binds via its SH3 domains to a proline-rich region (PRR) of p22 phox , the small subunit of cytochrome b 558 ; interaction plays a crucial role in the oxidase activation (20,21).…”

mentioning

confidence: 99%

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Novel Human Homologues of p47 and p67 Participate in Activation of Superoxide-producing NADPH Oxidases

Takeya

Ueno

Kami

et al. 2003

Journal of Biological Chemistry

336

316

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The catalytic core of a superoxide-producing NADPH oxidase (Nox) in phagocytes is gp91 phox /Nox2, a membrane-integrated protein that forms a heterodimer with p22 phox to constitute flavocytochrome b 558 . The cytochrome becomes activated by interacting with the adaptor proteins p47 phox and p67 phox as well as the small GTPase Rac. Here we describe the cloning of human cDNAs for novel proteins homologous to p47 phox and p67 phox , designated p41 nox and p51 nox , respectively; the former is encoded by NOXO1 (Nox organizer 1), and the latter is encoded by NOXA1 (Nox activator 1). The novel homologue p41 nox interacts with p22 phox via the two tandem SH3 domains, as does p47 phox . The protein p51 nox as well as p67 phox can form a complex with p47 phox and with p41 nox via the C-terminal SH3 domain and binds to GTPbound Rac via the N-terminal domain containing four tetratricopeptide repeat motifs. These bindings seem to play important roles, since p47 phox and p67 phox activate the phagocyte oxidase via the same interactions. Indeed, p41 nox and p51 nox are capable of replacing the corresponding classical homologue in activation of gp91 phox . Nox1, a homologue of gp91 phox , also can be activated in cells, when it is coexpressed with p41 nox and p51 nox , with p41 nox and p67 phox , or with p47 phox and p51 nox ; in the former two cases, Nox1 is partially activated without any stimulants added, suggesting that p41 nox is normally in an active state. Thus, the novel homologues p41 nox and p51 nox likely function together or in combination with a classical one, thereby activating the two Nox family oxidases.

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SH3 Domains

Mayer¹,

Saksela²

2004

Modular Protein Domains

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Diverse recognition of non-PxxP peptide ligands by the SH3 domains from p67phox, Grb2 and Pex13p

Cited by 166 publications

References 42 publications

A Regulated Adaptor Function of p40^phox: Distinct p67^phoxMembrane Targeting by p40^phoxand by p47^phox

A Regulated Adaptor Function of p40^phox: Distinct p67^phoxMembrane Targeting by p40^phoxand by p47^phox

Novel Human Homologues of p47 and p67 Participate in Activation of Superoxide-producing NADPH Oxidases

SH3 Domains

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Diverse recognition of non-PxxP peptide ligands by the SH3 domains from p67phox, Grb2 and Pex13p

Cited by 166 publications

References 42 publications

A Regulated Adaptor Function of p40phox: Distinct p67phoxMembrane Targeting by p40phoxand by p47phox

A Regulated Adaptor Function of p40phox: Distinct p67phoxMembrane Targeting by p40phoxand by p47phox

Novel Human Homologues of p47 and p67 Participate in Activation of Superoxide-producing NADPH Oxidases

SH3 Domains

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Product

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A Regulated Adaptor Function of p40^phox: Distinct p67^phoxMembrane Targeting by p40^phoxand by p47^phox

A Regulated Adaptor Function of p40^phox: Distinct p67^phoxMembrane Targeting by p40^phoxand by p47^phox