Insulin-induced tyrosine dephosphorylation of paxillin and focal adhesion kinase requires active phosphotyrosine phosphatase 1D

Ouwens, D.M.; Mikkers, H. M. M.; Zon, G.C.M. van der; Stein-Gerlach, Matthias; Ullrich, Axel; Maassen, J. Antonie

doi:10.1042/bj3180609

Cited by 44 publications

(46 citation statements)

References 67 publications

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“…Under the experimental conditions used in this study (cells were plated in complete medium) p125FAK was not tyrosine phosphorylated in response to cell-substrate interaction ( Figure 1a, lanes 9 ± 12). Previous studies have reported that serum components, especially insulin and insulin-like growth factors, stimulate the tyrosine dephosphorylation of p125FAK (Konstantopoulos and Clark, 1996;Ouwens et al, 1996;Pillay et al, 1995;Tobe et al, 1996). Thus, it is possible that tyrosine phosphorylation of p125FAK was not evident when cells were plated in serum-containing media due to the opposing in¯uences of serum growth factors such as insulin and IGF-1 (that promote dephosphorylation of focal adhesion proteins) and integrin engagement (that promote the tyrosine phosphorylation of focal adhesion proteins).…”

Section: Resultsmentioning

confidence: 99%

Rapid recruitment of p120RasGAP and its associated protein, p190RhoGAP, to the cytoskeleton during integrin mediated cell-substrate interaction

Sharma

1998

Oncogene

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The interaction of cells with their substrate triggers cascades of signal transduction that result in profound changes in cell morphology. The nature of these signals and how they are integrated to orchestrate changes in cell shape are beginning to be elucidated. In particular, adhesive interactions between cells and their substrate, mediated by cell-surface integrins and extracellular matrix (ECM) proteins, appear to result in massive rearrangement of the cell cytoskeleton via the small Gprotein, Rho. Here we show that in mouse ®broblasts, the interaction between cells and their substrate results in the rapid recruitment to the cytoskeleton of RasGAP (p120RasGAP), its associated protein of 190 kilodaltons, the GTPase activating protein for RhoA (p190RhoGAP) and the focal adhesion kinase (p125FAK). Similar results were obtained when cells were plated on ECM proteins, such as ®bronectin, suggesting that the phenomenon is integrin mediated. These studies suggest that in ®bro-blasts, cell-substrate interaction triggered by integrin engagement result in the recruitment to the cytoskeleton of signaling molecules such as p120RasGAP, p190Rho-GAP and p125FAK and may be involved in the formation of membrane cytoskeleton-associated signaling complexes that are important in cytoarchitectural reorganization.

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Section: Resultsmentioning

confidence: 99%

Rapid recruitment of p120RasGAP and its associated protein, p190RhoGAP, to the cytoskeleton during integrin mediated cell-substrate interaction

Sharma

1998

Oncogene

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“…We now propose that PTPs are targets for the ECM signals that regulate differentiation in mammary cells, possibly through direct interaction with proteins within adhesion complexes (53,54).…”

Section: Discussionmentioning

confidence: 99%

Regulation of Mammary Differentiation by Extracellular Matrix Involves Protein-tyrosine Phosphatases

Edwards¹,

Wilford²,

Liu³

et al. 1998

Journal of Biological Chemistry

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Extracellular matrix and growth factors cooperate to regulate signaling pathways and gene transcription in adherent cells. However, the mechanism of extracellular matrix signaling is poorly defined. In mammary gland, the expression of milk protein genes is controlled by cross-talk between signals derived from the basement membrane protein, laminin, and the lactogenic hormone, prolactin. Signals from basement membrane are transduced by ␤ 1 integrins and are required for prolactin to activate DNA binding of the milk protein gene transcription factor, Stat5. Here we show that basement membrane is necessary for tyrosine phosphorylation of the prolactin receptor and thus directly affects cytokine signaling and differentiation at the level of the plasma membrane. Prolactin does not induce tyrosine phosphorylation of its receptor, Jak2, or Stat5 in nondifferentiated breast epithelia cultured on collagen I, and we show that this is due to a vanadate-sensitive activity that inhibits the prolactin pathway. We suggest that protein-tyrosine phosphatases are novel targets for regulation by extracellular matrix and in mammary cells represent an additional control to the requirement of integrins for milk protein production.Cell behavior is controlled by a network of signals derived from growth and differentiation factors as well as from the local cellular environment. These signals are interpreted by appropriate receptors and converted into intracellular pathways that modulate transcriptional or post-transcriptional events. Migration, proliferation, survival, and differentiation are strongly influenced by cell interactions with the extracellular matrix (ECM) 1 (1). For example, integrins determine the activity of both Ras-mitogen-activated protein kinase and phosphatidylinositol 3Ј-kinase mediated growth factor responses, and cell-ECM interactions contribute to cyclin activation thereby regulating cell cycle entry (2-6). However, the mechanism for this ligand-induced signaling cross-talk has not been established. Many signal transduction pathways, including those conveyed by ECM-integrin interactions are controlled by protein-tyrosine kinases (PTKs) (7). Homeostasis of signaling requires negative regulation through protein-tyrosine phosphatases (PTPs) (8, 9), and these enzymes are therefore of potential significance in the control of ECM signaling.In the breast, epithelial cell interactions with basement membrane (BM) control the prolactin-dependent expression of milk protein genes (10, 11). Both laminin-1 and ␤ 1 integrins are required for differentiation of mammary cells (12, 13) and, together with prolactin, direct milk protein gene transcription. The molecular details of the prolactin signaling pathway were first described in the rat lymphoma cell line, Nb2, which requires prolactin for proliferation. Ligation of the prolactin receptor (PrlR) results in induction of the associated PTK activity, Jak2 (14 -16). This leads to activation of Stat transcription factors that recognize specific DNA sequence motifs in the promoters...

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“…In one study, insulininduced tyrosine dephosphorylation of FAK and paxillin was found to be mediated by protein phosphatase SHP2 (Ref. 53; but see also Ref. 17); SHP2 is also a known component of the EGF receptor signaling pathway (38).…”

Section: Discussionmentioning

confidence: 99%

Epidermal Growth Factor Modulates Tyrosine Phosphorylation of p130Cas

Ojaniemi¹,

Vuori

1997

Journal of Biological Chemistry

103

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Insulin-induced tyrosine dephosphorylation of paxillin and focal adhesion kinase requires active phosphotyrosine phosphatase 1D

Cited by 44 publications

References 67 publications

Rapid recruitment of p120RasGAP and its associated protein, p190RhoGAP, to the cytoskeleton during integrin mediated cell-substrate interaction

Rapid recruitment of p120RasGAP and its associated protein, p190RhoGAP, to the cytoskeleton during integrin mediated cell-substrate interaction

Regulation of Mammary Differentiation by Extracellular Matrix Involves Protein-tyrosine Phosphatases

Epidermal Growth Factor Modulates Tyrosine Phosphorylation of p130Cas

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