The Guanine Nucleotide Exchange Factor Tiam1 Affects Neuronal Morphology; Opposing Roles for the Small GTPases Rac and Rho

Leeuwen, Frank N. van; Kain, Hendrie E.T.; Kammen, Rob A. van der; Michiels, Frits; Kranenburg, Onno; Collard, John G.

doi:10.1083/jcb.139.3.797

Cited by 338 publications

(342 citation statements)

References 49 publications

(78 reference statements)

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“…In breast tumor cells, such as SP-1 cells, Tiam1 is detected as a 200-kD protein (Fig. 1), which is similar to the Tiam1 described in other cell types (Woods and Bryant 1991; Michiels et al 1995; Nobes and Hall 1995; Van Leeuwen et al 1995, Van Leeuwen et al 1997; Hordijk et al 1997; Stam et al 1997; Bourguignon et al 2000). Tiam1, isolated from SP-1 cells, is also capable of carrying out GDP/GTP exchange for Rac1 in vitro (Fig.…”

Section: Discussionsupporting

confidence: 64%

“…Rac1 acts downstream of Tiam1 signaling and regulates the function of several cell adhesion molecules such as the laminin receptor, α6β1 integrin (Van Leeuwen et al 1997), E-cadherin (Hordijk et al 1997), and the hyaluronan receptor, CD44 (Bourguignon et al 2000). Tiam1-Rac1 activation also has been shown to be stimulated by certain serum-derived growth activators (e.g., S1P and LPA) during T-lymphoma cell invasion (Stam et al 1998).…”

Section: Discussionmentioning

confidence: 99%

“…Apparently, various responses by Tiam1-catalyzed Rac1 signaling may be controlled by selective upstream activators (e.g., availability of certain cytoskeletal proteins [e.g., ankyrin], cell adhesion receptors [e.g., CD44, integrin or E-cadherin], growth activators [e.g., serum, S1P, or LPA] or extracellular matrix components [hyaluronic acid, collagen, or fibronectin, etc.]). Moreover, Tiam1 is found to be involved in promoting both Rac1- and RhoA-mediated pathways during neurite formation in nerve cells (Van Leeuwen et al 1997). The balance between Rac1 and RhoA determines a particular cellular morphology and migratory behavior (Sander et al 1999).…”

Section: Discussionmentioning

confidence: 99%

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Ankyrin–Tiam1 Interaction Promotes Rac1 Signaling and Metastatic Breast Tumor Cell Invasion and Migration

Bourguignon

Zhu

Shao

et al. 2000

The Journal of Cell Biology

116

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Tiam1 (T-lymphoma invasion and metastasis 1) is one of the known guanine nucleotide (GDP/GTP) exchange factors (GEFs) for Rho GTPases (e.g., Rac1) and is expressed in breast tumor cells (e.g., SP-1 cell line). Immunoprecipitation and immunoblot analyses indicate that Tiam1 and the cytoskeletal protein, ankyrin, are physically associated as a complex in vivo. In particular, the ankyrin repeat domain (ARD) of ankyrin is responsible for Tiam1 binding. Biochemical studies and deletion mutation analyses indicate that the 11–amino acid sequence between amino acids 717 and 727 of Tiam1 (717GEGTDAVKRS727L) is the ankyrin-binding domain. Most importantly, ankyrin binding to Tiam1 activates GDP/GTP exchange on Rho GTPases (e.g., Rac1).Using an Escherichia coli–derived calmodulin-binding peptide (CBP)–tagged recombinant Tiam1 (amino acids 393–728) fragment that contains the ankyrin-binding domain, we have detected a specific binding interaction between the Tiam1 (amino acids 393–738) fragment and ankyrin in vitro. This Tiam1 fragment also acts as a potent competitive inhibitor for Tiam1 binding to ankyrin. Transfection of SP-1 cell with Tiam1 cDNAs stimulates all of the following: (1) Tiam1–ankyrin association in the membrane projection; (2) Rac1 activation; and (3) breast tumor cell invasion and migration. Cotransfection of SP1 cells with green fluorescent protein (GFP)–tagged Tiam1 fragment cDNA and Tiam1 cDNA effectively blocks Tiam1–ankyrin colocalization in the cell membrane, and inhibits GDP/GTP exchange on Rac1 by ankyrin-associated Tiam1 and tumor-specific phenotypes. These findings suggest that ankyrin–Tiam1 interaction plays a pivotal role in regulating Rac1 signaling and cytoskeleton function required for oncogenic signaling and metastatic breast tumor cell progression.

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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Ankyrin–Tiam1 Interaction Promotes Rac1 Signaling and Metastatic Breast Tumor Cell Invasion and Migration

Bourguignon

Zhu

Shao

et al. 2000

The Journal of Cell Biology

116

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“…Several lines of evidence have suggested a functional antagonism between the Rac1/Cdc42 and RhoA-C subfamilies in controlling cytoskeletal structures (Kozma et al, 1997;Leeuwen et al, 1997;Moorman et al, 1999). As far as myogenesis is concerned, a similar balance between RhoG/Rac1/ Cdc42Hs and RhoA activities emerges in the light of the present study.…”

Section: Opposing Roles For Rhog/rac1/cdc42hs and Rhoa In Regulating supporting

confidence: 48%

Critical Activities of Rac1 and Cdc42Hs in Skeletal Myogenesis: Antagonistic Effects of JNK and p38 Pathways

Mériane

Roux

Primig

et al. 2000

MBoC

103

153

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The Rho family of GTP-binding proteins plays a critical role in a variety of cellular processes, including cytoskeletal reorganization and activation of kinases such as p38 and C-jun N-terminal kinase (JNK) MAPKs. We report here that dominant negative forms of Rac1 and Cdc42Hs inhibit the expression of the muscle-specific genes myogenin, troponin T, and myosin heavy chain in L6 and C2 myoblasts. Such inhibition correlates with decreased p38 activity. Active RhoA, RhoG, Rac1, and Cdc42Hs also prevent myoblast-to-myotube transition but affect distinct stages: RhoG, Rac1, and Cdc42Hs inhibit the expression of all muscle-specific genes analyzed, whereas active RhoA potentiates their expression but prevents the myoblast fusion process. We further show by two different approaches that the inhibitory effects of active Rac1 and Cdc42Hs are independent of their morphogenic activities. Rather, myogenesis inhibition is mediated by the JNK pathway, which also leads to a cytoplasmic redistribution of Myf5. We propose that although Rho proteins are required for the commitment of myogenesis, they differentially influence this process, positively for RhoA and Rac1/Cdc42Hs through the activation of the SRF and p38 pathways, respectively, and negatively for Rac1/Cdc42Hs through the activation of the JNK pathway. INTRODUCTIONThe development of skeletal muscle is a multistep process in which pluripotent mesodermal cells give rise to myoblasts that subsequently withdraw from the cell cycle and differentiate into plurinucleated myotubes. The earliest known markers for the skeletal muscle lineage are the four myogenic basic helix-loop-helix (bHLH) factors MyoD, Myf5, myogenin, and MRF4 (Molkentin and Olson, 1996;Arnold and Winter, 1998). During differentiation, myogenic bHLH factors activate muscle-specific genes (such as myosin light and heavy chains, troponin T, etc.) and coordinate withdrawal from the cell cycle (Lassar et al., 1994). In culture, differentiation of myocytes is induced when cells are exposed to medium containing a low concentration of mitogens (differentiation medium). These myogenic bHLH factors are targets of growth factor-signaling pathways that either negatively or positively regulate myogenic differentiation. In vivo experiments in mice have shown that sonic hedgehog and Wnt proteins coming from the dorsal neural tube control Myf5 expression, whereas MyoD is controlled by factors from the dorsal ectoderm (Munsterberg et al., 1995;Cossu et al., 1996;Stern et al., 1997). In addition, negative regulation by proteins such as BMP4, released by the lateral mesoderm, or proteins of the TGF␤ and FGF families plays an important role in this process (Pourquie et al., 1996).The Rho family of Ras-like GTPases are clustered in two distinct subgroups: the Rac/Cdc42 subgroup, which includes Rac1, Rac2, and Rac3, RhoG, Cdc42Hs, TC10, chp, and RhoH, and the Rho subgroup, in which RhoA, -B and -C, RhoD, RhoL, and Rnd1, Rnd2, and Rnd3 are found. Specific substitutions based on Ras studies result in the expression of proteins tha...

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“…Thus, currently the general picture is that Cdc42 activates Rac, which activates Rho (Matozaki et al, 2000). Evidence of mutual inhibition between Cdc42/Rac and Rho has also been found (Van Leeuwen et al, 1997;Sander et al, 1999;Firtel and Chung, 2000;Jiménez et al, 2000;Zondag et al, 2000;Caron, 2003).…”

Section: Spatial Localization and Crosstalk Of Rho Gtpasesmentioning

confidence: 78%

Polarization and Movement of Keratocytes: A Multiscale Modelling Approach

et al. 2006

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The Guanine Nucleotide Exchange Factor Tiam1 Affects Neuronal Morphology; Opposing Roles for the Small GTPases Rac and Rho

Cited by 338 publications

References 49 publications

Ankyrin–Tiam1 Interaction Promotes Rac1 Signaling and Metastatic Breast Tumor Cell Invasion and Migration

Ankyrin–Tiam1 Interaction Promotes Rac1 Signaling and Metastatic Breast Tumor Cell Invasion and Migration

Critical Activities of Rac1 and Cdc42Hs in Skeletal Myogenesis: Antagonistic Effects of JNK and p38 Pathways

Polarization and Movement of Keratocytes: A Multiscale Modelling Approach

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