Dissociation of Mitogenesis and Transforming Activity by C-Terminal Truncation of the Insulin-like Growth Factor-I Receptor

Surmacz, Ewa; Sell, Christian; Swantek, Jennifer L.; Kato, Hisatoyo; Roberts, Charles T.; LeRoith, Derek; Baserga, Renato

doi:10.1006/excr.1995.1168

Cited by 68 publications

(72 citation statements)

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“…In the lung, the IGF-IR is expressed in normal bronchial epithelial cells as well as in primary lung cancers and the ligand IGF-I appears to be the main autocrine growth factor in lung tumorigenesis. Mouse cells containing the wild-type IGF-IR grow anchorageindependent and express low levels of DBI-1 while mouse cells expressing the truncated IGF-IR grow anchorage-dependent and express elevated levels of DBI-1 (Surmacz et al, 1995;Ho III et al, 1998). Furthermore, expression of exogenous DBI-1 cDNA in mouse cells containing the wild-type IGF-IR antagonized IGF-I stimulation (Ho III et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Isolation of DICE1: A gene frequently affected by LOH and downregulated in lung carcinomas

et al. 1999

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Section: Discussionmentioning

confidence: 99%

Isolation of DICE1: A gene frequently affected by LOH and downregulated in lung carcinomas

et al. 1999

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“…Cell transformation is a complex process which is different from cell mitogenesis and involves a wide array of signaling events, such as the MAP kinase signal cascade and other signal pathway (7,20,28,29,41,50,51). In some cases, cell transformation is dissociated from mitogenesis (7,20,41).…”

Section: Discussionmentioning

confidence: 99%

“…It is well known that epidermal growth factor (EGF) can induce a high level of AP-1 activity and cell transformation as well as PI 3-kinase activity. Cell transformation is a complex process and much different from cell mitogenesis; in some cases, these two events are dissociated (7,20,29,41,51). Currently, little is known regarding whether PI 3-kinase and its products are involved in EGF-induced signal transduction to the transcriptional machinery of the nucleus and cell transformation.…”

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confidence: 99%

“…The cells were exposed to EGF, insulin, and EGF plus insulin for AP-1 induction with or without various concentrations of wortmannin or LY294002 for 24 h. The cells were extracted with lysis buffer, and luciferase activity was measured with a luminometer (monolight 2010). The results are expressed as relative AP-1 activity or relative luciferase units (3,41). PI 3-kinase assay.…”

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confidence: 99%

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Requirement for Phosphatidylinositol 3-Kinase in Epidermal Growth Factor-Induced AP-1 Transactivation and Transformation in JB6 P⁺ Cells

Huang

Dong

1996

Molecular and Cellular Biology

137

141

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Phosphatidylinositol 3-kinase (PI 3-kinase) is an important enzyme associated with a variety of receptors or proteintyrosine kinases and acts as a direct biochemical link between a novel phosphatidylinositol pathway and a number of receptor proteins, including the receptors for insulin or platelet-derived growth factor. This enzyme is a heterodimer of a 110-kDa (P110) catalytic subunit and an 85-kDa (P85) regulatory subunit (5). It can phosphorylate phosphatidylinositol (Ptdins), Ptdins(4) phosphate [Ptdins(4)P], or Ptdins(4,5) bisphosphate [Ptdins(4,5)P2] to produce Ptdins(3)P, Ptdins(3,4)P2, or Ptdins (3,4,5) trisphosphate [Ptdins(3,4,5)P3], respectively (2, 5, 52). Insulin or growth factor stimulation of the associated tyrosine kinase results in phosphorylation of the P85 subunit of PI 3-kinase. This phosphorylation is important for activation of PI 3-kinase (6).Several studies suggested that the PI 3-kinase products Ptdins(3,4)P2 and Ptdins(3,4,5)P3 are important regulators of cell proliferation (4, 21, 23). The introduction of the N-terminal SH 2 domain of the P85 subunit of PI 3-kinase into cells abrogates insulin-or insulin-like growth factor I (IGF-I)-stimulated DNA synthesis and prevents insulin stimulation of c-fos protein expression (21, 23). Other studies have shown that Ptdins(3,4)P2 and Ptdins(3,4,5)P3 levels are elevated in cells transformed by v-abl, v-src, and polyomavirus middle T, and decreased levels of these lipids correlate with impaired cell transformation by mutated forms of these oncogenes (4,16,47). Recently, it was reported that insulin could activate the Ras-Raf-mitogen-activated protein (MAP) kinase pathway by interacting with and activating its receptors (45, 53). Hu et al. suggest that activation of this Ras-MAP kinase pathway is critical for the effect of insulin on mitogenesis and c-fos expression (21). Others found that neither insulin nor phorbol ester regulation of phosphoenolpyruvate carboxykinase gene expression requires activation of the Ras-MAP kinase pathway but that PI 3-kinase is required in this event (17, 54). In contrast, Sakaue et al. demonstrated that neither the Ras-MAP kinase cascade nor PI 3-kinase may be required for insulinstimulated glycogen synthase activation in CHO cell lines (32). It is well known that epidermal growth factor (EGF) can induce a high level of AP-1 activity and cell transformation as well as PI 3-kinase activity. Cell transformation is a complex process and much different from cell mitogenesis; in some cases, these two events are dissociated (7,20,29,41,51). Currently, little is known regarding whether PI 3-kinase and its products are involved in EGF-induced signal transduction to the transcriptional machinery of the nucleus and cell transformation. We used the well-characterized mouse epidermal JB6 P ϩ (tumor promotion-sensitive) cells and addressed a novel function of PI 3-kinase in EGF-induced AP-1 transactivation and cell transformation. MATERIALS AND METHODSPlasmids and reagents. The AP-1 luciferase reporter plasmid (Col-Luc) and CMV-n...

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“…Deletion of the entire C-terminus at aa 1229 totally abrogated transforming function, without inhibiting mitogenic and antiapoptotic ability (Surmacz et al, 1995). The 'transforming domain' was mapped between residues 1245 and 1310, with Tyr 1251, Ser 1280-1283, His 1293, and Lys 1294 required for transformation (Hongo et al, 1996) (Figure 1).…”

Section: Igf-ir Structure-function Studiesmentioning

confidence: 99%

Growth factor receptors as therapeutic targets: strategies to inhibit the insulin-like growth factor I receptor

2003

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Dissociation of Mitogenesis and Transforming Activity by C-Terminal Truncation of the Insulin-like Growth Factor-I Receptor

Cited by 68 publications

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Isolation of DICE1: A gene frequently affected by LOH and downregulated in lung carcinomas

Isolation of DICE1: A gene frequently affected by LOH and downregulated in lung carcinomas

Requirement for Phosphatidylinositol 3-Kinase in Epidermal Growth Factor-Induced AP-1 Transactivation and Transformation in JB6 P⁺ Cells

Growth factor receptors as therapeutic targets: strategies to inhibit the insulin-like growth factor I receptor

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Dissociation of Mitogenesis and Transforming Activity by C-Terminal Truncation of the Insulin-like Growth Factor-I Receptor

Cited by 68 publications

References 0 publications

Isolation of DICE1: A gene frequently affected by LOH and downregulated in lung carcinomas

Isolation of DICE1: A gene frequently affected by LOH and downregulated in lung carcinomas

Requirement for Phosphatidylinositol 3-Kinase in Epidermal Growth Factor-Induced AP-1 Transactivation and Transformation in JB6 P+ Cells

Growth factor receptors as therapeutic targets: strategies to inhibit the insulin-like growth factor I receptor

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Requirement for Phosphatidylinositol 3-Kinase in Epidermal Growth Factor-Induced AP-1 Transactivation and Transformation in JB6 P⁺ Cells