Zizimin and Dock guanine nucleotide exchange factors in cell function and disease

Pakes, Nicholl K.; Veltman, Douwe M.; Williams, Robin S.B.

doi:10.4161/sgtp.22087

Cited by 14 publications

(13 citation statements)

References 44 publications

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“…23–25 DOCK RhoGEFs lack primary sequence homology with the DH domain and instead are characterized by a conserved Dock-homology region-2 (DHR-2; also called DOCKER, CZH2) that serves as the RhoGEF catalytic domain. DHR-2 domains exhibit no primary sequence homology to DH domains.…”

Section: The Discovery Of Rhogefs: Diverse In Numbers and Structurementioning

confidence: 99%

Rho guanine nucleotide exchange factors: regulators of Rho GTPase activity in development and disease

2013

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The aberrant activity of Ras homologous (Rho) family small GTPases (20 human members) has been implicated in cancer and other human diseases. However, in contrast to the direct mutational activation of Ras found in cancer and developmental disorders, Rho GTPases are activated most commonly by indirect mechanisms in disease. One prevalent mechanism involves aberrant Rho activation via the deregulated expression and/or activity of Rho family guanine nucleotide exchange factors (RhoGEFs). RhoGEFs promote formation of the active GTP-bound state of Rho GTPases. The largest family of RhoGEFs is comprised of the Dbl family RhoGEFs with 70 human members. The multitude of RhoGEFs that activate a single Rho GTPase reflect the very specific role of each RhoGEF in controlling distinct signaling mechanisms involved in Rho activation. In this review, we summarize the role of Dbl RhoGEFs in development and disease, with a focus on Ect2, Tiam1, Vav and P-Rex1/2.

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Section: The Discovery Of Rhogefs: Diverse In Numbers and Structurementioning

confidence: 99%

Rho guanine nucleotide exchange factors: regulators of Rho GTPase activity in development and disease

2013

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“…There are two distinct GEF families for Rho proteins: those of the diffuse B-cell lymphoma (Dbl) and dedicator of cytokinesis (Dock) families [10, 13, 14]. In the interest of space and to provide a focused review, emphasis will be on the Dbl GEFs.…”

Section: Introductionmentioning

confidence: 99%

RhoGEFs in Cell Motility: Novel Links Between Rgnef and Focal Adhesion Kinase

Miller¹,

Kleinschmidt²,

Schlaepfer³

2014

CMM

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Rho guanine exchange factors (GEFs) are a large, diverse family of proteins defined by their ability to catalyze the exchange of GDP for GTP on small GTPase proteins such as Rho family members. GEFs act as integrators from varied intra- and extracellular sources to promote spatiotemporal activity of Rho GTPases that control signaling pathways regulating cell proliferation and movement. Here we review recent studies elucidating roles of RhoGEF proteins in cell motility. Emphasis is placed on Dbl-family GEFs and connections to development, integrin signaling to Rho GTPases regulating cell adhesion and movement, and how these signals may enhance tumor progression. Moreover, RhoGEFs have additional domains that confer distinctive functions or specificity. We will focus on a unique interaction between Rgnef (also termed Arhgef28 or p190RhoGEF) and focal adhesion kinase (FAK), a non-receptor tyrosine kinase that controls migration properties of normal and tumor cells. This Rgnef-FAK interaction activates canonical GEF-dependent RhoA GTPase activity to govern contractility and also functions as a scaffold in a GEF-independent manner to enhance FAK activation. Recent studies have also brought to light the importance of specific regions within the Rgnef pleckstrin homology (PH) domain for targeting the membrane. As revealed by ongoing Rgnef-FAK investigations, exploring GEF roles in cancer will yield fundamental new information on the molecular mechanisms promoting tumor spread and metastasis.

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“…Although studies in mammalian cultured cells and Dictyostelium revealed the roles of Ziz in cell migration, development, cytokinesis and growth (Pakes et al, 2013), functions of Ziz in specific tissues and organs in multicellular organ- isms are still not fully understood. In the present study, we revealed that Ziz-knockdown in eye imaginal disc induced the decrease of pigments in adult compound eyes that are associated with increase of SPC-and TPC-like cells with aberrant morphology and orientation in pupal retinae.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, Zir appears to be necessary to activate Rac2 and Cdc42 during the cellular immune response in Drosophila (Sampson et al, 2012). Although studies in mammalian cultured cells and Dictyostelium revealed a role of Ziz in cell migration, development, cytokinesis and growth (Pakes et al, 2013), in vivo function of Ziz is still not fully understood.…”

Section: Introductionmentioning

confidence: 99%

<i>Drosophila</i> DOCK Family Protein Zizimin Involves in Pigment Cell Differentiation in Pupal Retinae

Ozasa

Morishita

Dang

et al. 2017

Cell Struct. Funct.

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Zizimin and Dock guanine nucleotide exchange factors in cell function and disease

Cited by 14 publications

References 44 publications

Rho guanine nucleotide exchange factors: regulators of Rho GTPase activity in development and disease

Rho guanine nucleotide exchange factors: regulators of Rho GTPase activity in development and disease

RhoGEFs in Cell Motility: Novel Links Between Rgnef and Focal Adhesion Kinase

<i>Drosophila</i> DOCK Family Protein Zizimin Involves in Pigment Cell Differentiation in Pupal Retinae

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