Lysophosphatidate-induced cell proliferation: Identification and dissection of signaling pathways mediated by G proteins

Corven, E J van; Groenink, Alida; Jalink, Kees; Eichholtz, Thomas; Moolenaar, Wouter H.

doi:10.1016/0092-8674(89)90868-4

Cited by 808 publications

(620 citation statements)

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“…In addition, LPA induced little increase of this parameter in FAK(7/7) cells, whereas it did *twofold increase in FAK(+/+) cells (Figure 4a, right panel). LPA has been shown to induce polyphosphoinositide breakdown (van Corven et al, 1989;Moolenaar, 1994). LPA (5 mM) stimulated 1,4,5-inositol triphosphate (IP3) production to the same extent in the FAK(7/7) cells as compared to that observed in FAK(+/+) cells (FAK(+/+): basal, 7+1 pmol/10 6 cells; LPA-stimulated, 18+3 pmol/10 6 cells, FAK(7/7) cells: basal, 8+2 pmol/10 6 cells; LPA-stimulated, 20+3 pmol/10 6 cells (mean+s.e., n=3).…”

Section: Resultsmentioning

confidence: 99%

“…These actions appear to be mediated by both pertussis toxin (PTX) sensitiveand PTX-insensitive G proteins; the former may stimulate RAS ± MAP kinase activation and inhibit adenylate cyclase, whereas the latter may induce polyphosphoinositide breakdown (van Corven et al, 1989;Hordijk et al, 1994;Moolenaar, 1994). In addition, the small GTP-binding proteins RHO (Narumiya, 1993) is implicated in LPA-induced assembly of focal adhesions and the formation of actin stress ®bers (Ridley and Hall, 1992;Nobes and Hall, 1995).…”

Section: Introductionmentioning

confidence: 99%

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Lysophosphatidic acid-induced association of SHP-2 with SHPS-1: roles of RHO, FAK, and a SRC family kinase

et al. 1998

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SHPS-1 is an *120 kDa glycosylated receptor like protein that contains three immunoglobulin-like domains in its extracellular region as well as four potential tyrosine phosphorylation and SRC homology 2 (SH2) domain binding sites in its cytoplasmic region. Lysophosphatidic acid (LPA) stimulated the rapid tyrosine phosphorylation of SHPS-1 and its subsequent association with SHP-2, a protein tyrosine phosphatase containing SH2 domains in Rat-1 ®broblasts. LAP-induced tyrosine phosphorylation of SHPS-1 was inhibited by Clostridium botulinum C3 exoenzyme (which inactivates RHO) but not by pertussis toxin. The protein kinase C activator phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA) also stimulated tyrosine phosphorylation of SHPS-1; however, down-regulation of protein kinase C by prolonged exposure of cells to TPA did not a ect LAP-induced tyrosine phosphorylation of SHPS-1. LPA-induced tyrosine phosphorylation of SHPS-1 was markedly reduced in either focal adhesion kinase (FAK)-de®cient mouse cells or CHO cells overexpressing the tyrosine kinase CSK. Overexpression of a catalytically inactivate SHP-2 markedly inhibited MAP kinase activation in response to low concentrations of LPA in CHO cells, whereas overexpression of a wild-type SHPS-1 did enhance this e ect of LPA. Furthermore, MAP kinase activation in response to a low concentration of LPA was inhibited by botulinum C3 exoenzyme. These results indicate that LPA-induced tyrosine phosphorylation of SHPS-1 and its association with SHP-2 may be mediated by a RHO-dependent pathway that includes FAK and a SRC family kinase. Thus, in addition to its role in receptor tyrosine kinase-mediated MAP kinase activation, the formation of a complex between SHPS-1 and SHP-2 may, in part, play an important role in the activation of MAP kinase in response to low concentrations of LPA.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Lysophosphatidic acid-induced association of SHP-2 with SHPS-1: roles of RHO, FAK, and a SRC family kinase

et al. 1998

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“…The decrease in PA concentrations caused by cAMP could inhibit cell division partly by decreasing Raf activation (Ghosh et al, 1996). Conversely, diminished basal and stimulated cAMP concentrations in ras-transformed cells (Tagliaferri et al, 1988;Davies et al, 1989;Wakelam et al, 1991) may result partly from the large increase in PA concentrations ( Figure 2 and Table 1) which could inhibit adenylyl cyclase (Murayama and Ui, 1987;van Corven et al, 1989;GoÂ mez-MunÄ oz et al, 1994). Increased PA concentrations in ras-transformed fibroblasts could also alter morphology since PA, or its derivative lysoPA, can activate actin polymerization involving Rho (Ha and Exton, 1993;Moolenaar, 1995;Cross et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

“…PA stimulates superoxide generation in neutrophils (Rossi et al, 1990;Bauldry et al, 1991), and increases the activities of cytosolic protein kinase(s) (Bocckino et al, 1991), protein kinase C-z (Limotola et al, 1994), phosphatidylinositol-4-phosphate kinase (Moritz et al, 1992), andPLC-g (Jones andCarpenter, 1993). Exogenous PA and lyso-PA inhibit adenylate cyclase (Murayama and Ui, 1987;van Corven et al, 1989;GoÂ mez-MunÄ oz et al, 1994) and increase arachidonate concentrations (Moolenaar, 1995), tyrosine kinase activities (Moolenaar, 1995) and mitogen-activated protein (MAP) kinase activities in a variety of cells (Howe and Marshall, 1993;Moolenaar, 1995;GoÂ mezMunÄ oz et al, 1995). Exogenous PA and lyso-PA also activate PLD Moolenaar, 1995) such that external PA is able to generate intracellular PA.…”

mentioning

confidence: 99%

Increased concentrations of phosphatidate, diacylglycerol and ceramide in ras- and tyrosine kinase (fps)-transformed fibroblasts

et al. 1997

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Concentrations of the bioactive lipids, phosphatidate and diacylglycerol, increased with time in culture in ras-and tyrosine kinase (fps)-transformed ®broblasts but not in control ®broblasts. On Day 3, diacylglycerol and phosphatidate concentrations were about 3.3-and 5.5-fold higher respectively in the ras-transformed compared to control ®broblasts. These concentrations in fpstransformed ®broblasts were increased about twofold. The changes in phosphatidate and diacylglycerol resulted from enhanced phospholipid turnover rather than from synthesis de novo. The increased ratio of phosphatidate to diacylglycerol is explained by decreased activities of two distinct phosphatidate phosphohydrolases and increased diacylglycerol kinase in ras-transformed ®bro-blasts. Ceramide concentrations were about 2.5-and threefold higher in the fps-and ras-transformed cells respectively on Day 3 compared to the controls. Incubating control ®broblasts from Days 1 to 3 with phosphatidylcholine-speci®c phospholipase C increased diacylglycerol, phosphatidate and ceramide concentrations, and decreased Mg 2+ -independent-phosphatidate phosphohydrolase activity. 8-(4-chlorophenylthio)-cAMP had a cytostatic e ect in ras-transformed cells, it decreased the concentrations of phosphatidate and diacylglycerol, but increased that of ceramide. The consequences of increased ceramide and phosphatidate concentrations in ras-transformed cells are discussed in relation to signal transduction, cell division and the transformed phenotype.

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“…For example, Pouyssegur and colleagues noted that DNA-synthesis in CHO cells in response to thrombin was blocked by Ptx treatment, whereas the proliferative response to PDGF was Ptx-insensitive (Chambard et al, 1987;Pouyssegur et al, 1988). A similar approach led to the discovery that one of the most potent mitogens present in serum, lysophosphatidic acid (LPA), a simple naturally occurring phospholipid, was also acting on the G protein-linked class of receptors (van Corven et al, 1989). Many other Ptx sensitive mitogens were subsequently identi®ed (see for a review).…”

Section: G Protein-coupled Receptors and Cell Proliferationmentioning

confidence: 99%

Cell growth control by G protein-coupled receptors: from signal transduction to signal integration

1998

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Lysophosphatidate-induced cell proliferation: Identification and dissection of signaling pathways mediated by G proteins

Cited by 808 publications

References 35 publications

Lysophosphatidic acid-induced association of SHP-2 with SHPS-1: roles of RHO, FAK, and a SRC family kinase

Lysophosphatidic acid-induced association of SHP-2 with SHPS-1: roles of RHO, FAK, and a SRC family kinase

Increased concentrations of phosphatidate, diacylglycerol and ceramide in ras- and tyrosine kinase (fps)-transformed fibroblasts

Cell growth control by G protein-coupled receptors: from signal transduction to signal integration

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