Different transforming growth factor-α species are derived from a glycosylated and palmitoylated transmembrane precursor

Bringman, Timothy S.; Lindquist, Patricia B.; Derynck, Rik

doi:10.1016/0092-8674(87)90194-2

Cited by 248 publications

(149 citation statements)

References 43 publications

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“…In CHO-K1 cells, EGFR is not expressed (45). We demonstrated that EGF does not activate ERK in CHO-K1 cells, as anticipated because of the lack of receptor; however, uPA did activate ERK.…”

Section: Fig 2 Rac1 Activation By Upar Overexpression In Cos-7 Cellsupporting

confidence: 75%

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Epidermal Growth Factor Receptor-dependent and -independent Cell-signaling Pathways Originating from the Urokinase Receptor

Thomas

O'Donnell

et al. 2003

Journal of Biological Chemistry

125

121

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Urokinase-type plasminogen activator (uPA) and vitronectin activate cell-signaling pathways by binding to the uPA receptor (uPAR). Because uPAR is glycosylphosphatidylinositol-anchored, the signaling receptor is most likely a uPAR-containing multiprotein complex. This complex may be heterogeneous within a single cell and among different cell types. The goal of this study was to elucidate the role of the EGF receptor (EGFR) as a component of the uPAR-signaling machinery. uPA activated extracellular signal-regulated kinase (ERK) in COS-7 cells and in COS-7 cells that overexpress uPAR, and this response was blocked by the EGFR inhibitor, tyrphostin AG1478, implicating the EGFR in the pathway that links uPAR to ERK. By contrast, Rac1 activation, which occurred as a result of uPAR overexpression, was EGFR-independent. COS-7 cell migration was stimulated, in an additive manner, by uPAR-dependent pathways leading to ERK and Rac1. AG1478 inhibited only the ERK-dependent component of the response. CHO-K1 cells do not express EGFR; however, these cells demonstrated ERK activation in response to uPA, indicating the presence of an EGFR-independent alternative pathway. As anticipated, this response was insensitive to AG1478. When CHO-K1 cells were transfected to express EGFR or a kinase-inactive mutant of EGFR, ERK activation in response to uPA was unchanged; however, the EGFR-expressing cells acquired sensitivity to AG1478. We conclude that the EGFR may function as a transducer of the signal from uPAR to ERK, but not Rac1. In the absence of EGFR, an alternative pathway links uPAR to ERK; however, this pathway is apparently silenced by EGFR expression.

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“…In CHO-K1 cells, EGFR is not expressed (45). We demonstrated that EGF does not activate ERK in CHO-K1 cells, as anticipated because of the lack of receptor; however, uPA did activate ERK.…”

Section: Fig 2 Rac1 Activation By Upar Overexpression In Cos-7 Cellsupporting

confidence: 75%

“…An EGFR-independent Pathway for ERK Activation by uPA-CHO-K1 cells express cell-surface uPAR but not EGFR (45). Thus, we chose this cell line to further probe the dependence on EGFR for uPAR-signaling to ERK.…”

Section: Role Of Egfr In Upar-stimulated Cos-7 Cellmentioning

confidence: 99%

Epidermal Growth Factor Receptor-dependent and -independent Cell-signaling Pathways Originating from the Urokinase Receptor

Thomas

O'Donnell

et al. 2003

Journal of Biological Chemistry

125

121

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“…It is released from the cell following cleavage from a 160 amino acid transmembrane precursor (Derynck et al, 1988;Gentry et al, 1987;Lee et al, 1985;Mueller et al, 1989). This precursor is glycosylated and palmitoylated and has biological activity (Bringman et al, 1987;Massague, 1990). It is preceded by an amino terminal region which contains N-and O-linked glycosylation sites which are responsible for the size heterogeneity of the TGFa precursor (Linsley et al, 1985;Luetteke et al, 1988;Teixido and Massague, 1988).…”

Section: Introductionmentioning

confidence: 99%

Defective cleavage of membrane bound TGFα leads to enhanced activation of the EGF receptor in malignant cells

Yang

Jiang

et al. 2000

Oncogene

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“…TGF-a with a molecular size of 6kDa has been purified from transformed rodent and human cells, sequenced and cloned (Derynck et al, 1984;Lee et al, 1985a). On the other hand, TGF-a-like activity of substances with different molecular sizes has been detected in the spent media and tumour cell extracts in several tumour cells (Bringman et al, 1987;Teixido et al, 1987). We also have demonstrated that TGF-a produced by human lung adenocarcinoma cell lines has multiple molecular sizes; these were considered to be macromolecular TGF-a, TGF-a(I-50) and molecules with lower molecular sizes (Imanishi et al, 1988).…”

Section: Discussionmentioning

confidence: 99%

Production of transforming growth factor-α in human tumour cell lines

Imanishi¹,

Yamaguchi²,

Suzuki³

et al. 1989

Br J Cancer

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Different transforming growth factor-α species are derived from a glycosylated and palmitoylated transmembrane precursor

Cited by 248 publications

References 43 publications

Epidermal Growth Factor Receptor-dependent and -independent Cell-signaling Pathways Originating from the Urokinase Receptor

Epidermal Growth Factor Receptor-dependent and -independent Cell-signaling Pathways Originating from the Urokinase Receptor

Defective cleavage of membrane bound TGFα leads to enhanced activation of the EGF receptor in malignant cells

Production of transforming growth factor-α in human tumour cell lines

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