An Electrostatic Steering Mechanism of Cdc42 Recognition by Wiskott-Aldrich Syndrome Proteins

Hemsath, Lars; Dvorský, Radovan; Fiegen, Dennis; Carlier, Marie‐France; Ahmadian, Mohammad Réza

doi:10.1016/j.molcel.2005.08.036

Cited by 117 publications

(182 citation statements)

References 49 publications

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“…The results indicated that the stabilities of the two proteins are rather similar. Also, the x-ray crystal structure of the edited RhoQ protein compared with the previously reported WT RhoQ protein structure (Hemsath et al, 2005) indicated that there are no changes in the global or local structural folds (Fig. 4 B).…”

Section: Protein Structure Of Edited Rhoqmentioning

confidence: 57%

RNA Editing in RHOQ Promotes Invasion Potential in Colorectal Cancer

Han¹,

Kim²,

Shin³

et al. 2014

J Cell Biol

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Section: Protein Structure Of Edited Rhoqmentioning

confidence: 57%

RNA Editing in RHOQ Promotes Invasion Potential in Colorectal Cancer

Han¹,

Kim²,

Shin³

et al. 2014

J Cell Biol

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“…It would therefore be predicted that components of the Cdo complex would cluster at sites of active Ncad ligation. To test this notion, Ncad ectodomain-coated microspheres were allowed to settle onto adherent NIH 3T3 cells that transiently expressed fluorescently tagged forms of Ncad, Cdo, JLP, Bnip-2, or the Cdc42-binding domain of N-Wasp (wGBD), which inter- acts specifically with active, GTP-bound Cdc42 (30). Cadherincoated beads attach to cells via cognate cellular cadherins, and additional cellular proteins that cluster at these sites of adhesion can be visualized as a fluorescent signal surrounding the bead (31)(32)(33).…”

Section: Resultsmentioning

confidence: 99%

N-cadherin ligation, but not Sonic hedgehog binding, initiates Cdo-dependent p38α/β MAPK signaling in skeletal myoblasts

Lü

Krauss

2010

Proc. Natl. Acad. Sci. U.S.A.

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The p38α/β mitogen-activated protein kinase (MAPK) pathway promotes muscle-specific gene expression and myoblast differentiation but how pathway activity is initiated during these processes is poorly understood. During myoblast differentiation, the intracellular region of the promyogenic cell surface protein Cdo (also known as Cdon) binds to Bnip-2 and JLP, scaffold proteins for Cdc42 and p38α/β MAPK, respectively. The Bnip-2/Cdc42 and JLP/p38α/β complexes associate in a Cdo-dependent manner, resulting in Bnip-2/Cdc42-dependent p38α/β activation and stimulation of cell differentiation. Although the Cdo ectodomain binds to several different proteins, it is unclear how Cdo-dependent p38α/β activation is initiated. In myoblasts, Cdo interacts with the cell–cell adhesion molecule N-cadherin. Cdo also binds directly to the secreted morphogen Sonic hedgehog (Shh) to promote Shh pathway signaling. We report here that N-cadherin ligation activates p38α/β in myoblasts in a Cdo-, Bnip-2-, and JLP-dependent manner. Furthermore, these proteins and activated Cdc42 cluster at sites of N-cadherin ligation. In contrast, neither JLP nor Bnip-2 is associated with Cdo bound to Shh, and Shh does not activate p38α/β in myoblasts. Taken together, these results link cadherin-based cell–cell adhesion to a defined signaling pathway (Cdo → p38α/β) that directly regulates a cell-type-specific differentiation program. Furthermore, they are consistent with a model whereby Cdo serves as a multifunctional coreceptor with mechanistically distinct roles in multiple signaling pathways.

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“…In fact, the N-WASP domain does not localize to the plasma membrane when expressed in yeast, and it cannot restore signaling when used to replace the Ste20 BR domain (S. Takahashi and P. M. Pryciak, unpublished data). Second, the polybasic domain of N-WASP has been proposed to interact transiently with acidic residues in Cdc42 and thereby accelerate CRIB-Cdc42 binding by "electrostatic steering" (Hemsath et al, 2005). In contrast, it seems unlikely that the yeast BR domains need to directly contact Cdc42, given the ability of PH domains to substitute for their function.…”

Section: Synergistic Protein-protein and Protein-membrane Interactionsmentioning

confidence: 99%

Identification of Novel Membrane-binding Domains in Multiple Yeast Cdc42 Effectors

Takahashi

Pryciak

2007

MBoC

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The Rho-type GTPase Cdc42 is a central regulator of eukaryotic cell polarity and signal transduction. In budding yeast, Cdc42 regulates polarity and mitogen-activated protein (MAP) kinase signaling in part through the PAK-family kinase Ste20. Activation of Ste20 requires a Cdc42/Rac interactive binding (CRIB) domain, which mediates its recruitment to membrane-associated Cdc42. Here, we identify a separate domain in Ste20 that interacts directly with membrane phospholipids and is critical for its function. This short region, termed the basic-rich (BR) domain, can target green fluorescent protein to the plasma membrane in vivo and binds PIP 2 -containing liposomes in vitro. Mutation of basic or hydrophobic residues in the BR domain abolishes polarized localization of Ste20 and its function in both MAP kinase-dependent and independent pathways. Thus, Cdc42 binding is required but is insufficient; instead, direct membrane binding by Ste20 is also required. Nevertheless, phospholipid specificity is not essential in vivo, because the BR domain can be replaced with several heterologous lipid-binding domains of varying lipid preferences. We also identify functionally important BR domains in two other yeast Cdc42 effectors, Gic1 and Gic2, suggesting that cooperation between protein-protein and protein-membrane interactions is a prevalent mechanism during Cdc42-regulated signaling and perhaps for other dynamic localization events at the cell cortex.

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An Electrostatic Steering Mechanism of Cdc42 Recognition by Wiskott-Aldrich Syndrome Proteins

Cited by 117 publications

References 49 publications

RNA Editing in RHOQ Promotes Invasion Potential in Colorectal Cancer

RNA Editing in RHOQ Promotes Invasion Potential in Colorectal Cancer

N-cadherin ligation, but not Sonic hedgehog binding, initiates Cdo-dependent p38α/β MAPK signaling in skeletal myoblasts

Identification of Novel Membrane-binding Domains in Multiple Yeast Cdc42 Effectors

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