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Joan S. Brugge

Bio: Joan S. Brugge is an academic researcher from Harvard University. The author has contributed to research in topics: Proto-oncogene tyrosine-protein kinase Src & Phosphorylation. The author has an hindex of 115, co-authored 286 publications receiving 47965 citations. Previous affiliations of Joan S. Brugge include Howard Hughes Medical Institute & Massachusetts Institute of Technology.


Papers
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Journal ArticleDOI
14 Apr 1995-Science
TL;DR: Recent advances in understanding of intracellular signal transduction pathways regulated by the integrin family of adhesion receptors are focused on.
Abstract: Adhesive interactions play critical roles in directing the migration, proliferation, and differentiation of cells; aberrations in such interactions can lead to pathological disorders. These adhesive interactions, mediated by cell surface receptors that bind to ligands on adjacent cells or in the extracellular matrix, also regulate intracellular signal transduction pathways that control adhesion-induced changes in cell physiology. Though the extracellular molecular interactions involving many adhesion receptors have been well characterized, the adhesion-dependent intracellular signaling events that regulate these physiological alterations have only begun to be elucidated. This article will focus on recent advances in our understanding of intracellular signal transduction pathways regulated by the integrin family of adhesion receptors.

3,000 citations

Journal ArticleDOI
TL;DR: This chapter reviews the evidence implicating Src family kinases in specific receptor pathways and describes the mechanisms leading to their activation, the targets that interact with these kinases, and the biological events that they regulate.
Abstract: Src family protein tyrosine kinases are activated following engagement of many different classes of cellular receptors and participate in signaling pathways that control a diverse spectrum of receptor-induced biological activities. While several of these kinases have evolved to play distinct roles in specific receptor pathways, there is considerable redundancy in the functions of these kinases, both with respect to the receptor pathways that activate these kinases and the downstream effectors that mediate their biological activities. This chapter reviews the evidence implicating Src family kinases in specific receptor pathways and describes the mechanisms leading to their activation, the targets that interact with these kinases, and the biological events that they regulate.

2,455 citations

Journal ArticleDOI
01 Jul 2003-Methods
TL;DR: A collection of protocols to culture MCF-10A cells, to establish stable pools expressing a gene of interest via retroviral infection, as well as to grow and analyzeMCF- 10A cells in three-dimensional basement membrane culture are provided.

1,957 citations

Journal ArticleDOI
TL;DR: The important features of epithelial structures grown in 3D basement membrane cultures, and how such models have been used to investigate the mechanisms associated with tumour initiation and progression are reviewed.
Abstract: Little is known about how the genotypic and molecular abnormalities associated with epithelial cancers actually contribute to the histological phenotypes observed in tumours in vivo. 3D epithelial culture systems are a valuable tool for modelling cancer genes and pathways in a structurally appropriate context. Here, we review the important features of epithelial structures grown in 3D basement membrane cultures, and how such models have been used to investigate the mechanisms associated with tumour initiation and progression.

1,030 citations

Journal ArticleDOI
17 Dec 1992-Nature
TL;DR: The results suggest that She tyrosine phosphorylation can couple tyosine kinases to Grb2/Sem-5, through formation of a Shc-Grb2-Sem- 5 complex, and thereby regulate the mammalian Ras signalling pathway.
Abstract: THE mammalian shc gene encodes two overlapping, widely expressed proteins of 46 and 52K, with a carboxy-terminal SH2 domain that binds activated growth factor receptors, and a more amino-terminal glycine/proline-rich region1. These shc gene products (Shc) are transforming when overexpressed in fibroblasts1. Shc proteins become phosphorylated on tyrosine in cells stimulated with a variety of growth factors1, and in cells transformed by v-src (ref. 2), suggesting that they are tyrosine kinase targets that control a mitogenic signalling pathway. Here we report that tyrosine-phosphorylated She proteins form a specific complex with a non-phosphorylated 23K polypeptide encoded by the grb2/sem-5 gene3,4. The grb2/sem-5 gene product itself contains an SH2 domain, which mediates binding to Shc, and is implicated in activation of the Ras guanine nucleotide-binding protein by tyrosine kinases in both Caenorhabditis elegans and mammalian cells3,4. Consistent with a role in signalling through Ras, shc overexpression induced Ras-dependent neurite outgrowth in PC 12 cells. These results suggest that She tyrosine phosphorylation can couple tyrosine kinases to Grb2/Sem-5, through formation of a Shc-Grb2/Sem-5 complex, and thereby regulate the mammalian Ras signalling pathway.

987 citations


Cited by
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Journal ArticleDOI
20 Sep 2002-Cell
TL;DR: Current structural and cell biological data suggest models for how integrins transmit signals between their extracellular ligand binding adhesion sites and their cytoplasmic domains, which link to the cytoskeleton and to signal transduction pathways.

8,275 citations

Journal ArticleDOI
13 Oct 2000-Cell
TL;DR: Understanding of the complex signaling networks downstream from RTKs and how alterations in these networks are translated into cellular responses provides an important context for therapeutically countering the effects of pathogenic RTK mutations in cancer and other diseases.

7,056 citations

Journal ArticleDOI
TL;DR: When epidermal growth factor and its relatives bind the ErbB family of receptors, they trigger a rich network of signalling pathways, culminating in responses ranging from cell division to death, motility to adhesion.
Abstract: When epidermal growth factor and its relatives bind the ErbB family of receptors, they trigger a rich network of signalling pathways, culminating in responses ranging from cell division to death, motility to adhesion. The network is often dysregulated in cancer and lends credence to the mantra that molecular understanding yields clinical benefit: over 25,000 women with breast cancer have now been treated with trastuzumab (Herceptin), a recombinant antibody designed to block the receptor ErbB2. Likewise, small-molecule enzyme inhibitors and monoclonal antibodies to ErbB1 are in advanced phases of clinical testing. What can this pathway teach us about translating basic science into clinical use?

6,462 citations

Journal ArticleDOI
TL;DR: The reprogramming of gene expression during EMT, as well as non-transcriptional changes, are initiated and controlled by signalling pathways that respond to extracellular cues, and the convergence of signalling pathways is essential for EMT.
Abstract: The transdifferentiation of epithelial cells into motile mesenchymal cells, a process known as epithelial-mesenchymal transition (EMT), is integral in development, wound healing and stem cell behaviour, and contributes pathologically to fibrosis and cancer progression. This switch in cell differentiation and behaviour is mediated by key transcription factors, including SNAIL, zinc-finger E-box-binding (ZEB) and basic helix-loop-helix transcription factors, the functions of which are finely regulated at the transcriptional, translational and post-translational levels. The reprogramming of gene expression during EMT, as well as non-transcriptional changes, are initiated and controlled by signalling pathways that respond to extracellular cues. Among these, transforming growth factor-β (TGFβ) family signalling has a predominant role; however, the convergence of signalling pathways is essential for EMT.

6,036 citations