Author
Richard K. Assoian
Other affiliations: Columbia University, Wistar Institute, National Institutes of Health ...read more
Bio: Richard K. Assoian is an academic researcher from University of Pennsylvania. The author has contributed to research in topics: Cyclin A & Cyclin D1. The author has an hindex of 58, co-authored 122 publications receiving 20068 citations. Previous affiliations of Richard K. Assoian include Columbia University & Wistar Institute.
Papers published on a yearly basis
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TL;DR: Further data are obtained to support a role for TGF-beta as an intrinsic mediator of collagen formation: conditioned media obtained from activated human tonsillar T lymphocytes contain greatly elevated levels of T GF-beta compared tomedia obtained from unactivated lymphocytes.
Abstract: Transforming growth factor type beta (TGF-beta), when injected subcutaneously in newborn mice, causes formation of granulation tissue (induction of angiogenesis and activation of fibroblasts to produce collagen) at the site of injection. These effects occur within 2-3 days at dose levels than 1 microgram. Parallel in vitro studies show that TGF-beta causes marked increase of either proline or leucine incorporation into collagen in either an NRK rat fibroblast cell line or early passage human dermal fibroblasts. Epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) do not cause these same in vivo and in vitro effects; in both rat and human fibroblast cultures, EGF antagonizes the effects of TGF-beta on collagen formation. We have obtained further data to support a role for TGF-beta as an intrinsic mediator of collagen formation: conditioned media obtained from activated human tonsillar T lymphocytes contain greatly elevated levels of TGF-beta compared to media obtained from unactivated lymphocytes. These activated media markedly stimulate proline incorporation into collagen in NRK cells; this effect is blocked by a specific antibody to TGF-beta. The data are all compatible with the hypothesis that TGF-beta is an important mediator of tissue repair.
2,860 citations
TL;DR: The cDNA sequence indicates that the 112-amino acid monomeric form of the natural TGF-β homodimer is derived proteolytically from a much longer precursor polypeptide which may be secreted.
Abstract: The partial amino-acid sequence of purified human transforming growth factor-beta (TGF-beta) was used to identify a series of cDNA clones encoding the protein. The cDNA sequence indicates that the 112-amino acid monomeric form of the natural TGF-beta homodimer is derived proteolytically from a much longer precursor polypeptide which may be secreted. TGF-beta messenger RNA is synthesized in various normal and transformed cells.
1,716 citations
TL;DR: The results show that platelets contain a type beta transforming growth factor, which is distinct from platelet-derived growth factor and elicits 50% of its maximal biological response at concentrations less than 5 x 10(-12) M.
1,527 citations
TL;DR: TGF-beta's marked ability to enhance formation of connective tissue in vivo suggests several therapeutic applications.
Abstract: Transforming growth factor-beta (TGF-beta) is a multifunctional peptide that controls proliferation, differentiation, and other functions in many cell types. Many cells synthesize TGF-beta and essentially all of them have specific receptors for this peptide. TGF-beta regulates the actions of many other peptide growth factors and determines a positive or negative direction of their effects. Its marked ability to enhance formation of connective tissue in vivo suggests several therapeutic applications.
1,194 citations
TL;DR: It is shown that cosecretion of TGF-beta and its monocyte/macrophage-derived binding protein may modulate growth factor action and that monocytic expression of other growth factor genes, such as the B chain of platelet-derived growth factor, is not constitutive and requires activation.
Abstract: Alveolar macrophages activated with concanavalin A and peripheral blood monocytes activated with lipopolysaccharide secrete type beta transforming growth factor (TGF-beta). There is minimal TGF-beta secretion in unactivated monocytes, even though TGF-beta mRNA is expressed in these cells at a level similar to that in activated, lipopolysaccharide-treated cultures. U937 lymphoma cells, which have monocytic characteristics, also express mRNA for TGF-beta. Freshly isolated monocytes, both control and lipopolysaccharide-treated, secrete an acid-labile binding protein that inhibits TGF-beta action. We conclude the following: (i) that expression of TGF-beta mRNA is unrelated to monocyte activation, (ii) that secretion of TGF-beta is induced by monocyte activation, and (iii) that cosecretion of TGF-beta and its monocyte/macrophage-derived binding protein may modulate growth factor action. In contrast, monocytic expression of other growth factor genes, such as the B chain of platelet-derived growth factor, is not constitutive and requires activation.
986 citations
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TL;DR: Atherosclerosis is an inflammatory disease as discussed by the authors, and it is a major cause of death in the United States, Europe, and much of Asia, despite changes in lifestyle and use of new pharmacologic approaches to lower plasma cholesterol concentrations.
Abstract: Atherosclerosis is an inflammatory disease. Because high plasma concentrations of cholesterol, in particular those of low-density lipoprotein (LDL) cholesterol, are one of the principal risk factors for atherosclerosis,1 the process of atherogenesis has been considered by many to consist largely of the accumulation of lipids within the artery wall; however, it is much more than that. Despite changes in lifestyle and the use of new pharmacologic approaches to lower plasma cholesterol concentrations,2,3 cardiovascular disease continues to be the principal cause of death in the United States, Europe, and much of Asia.4,5 In fact, the lesions of atherosclerosis represent . . .
19,881 citations
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
TL;DR: The transforming growth factor beta (TGF-beta) family of growth factors control the development and homeostasis of most tissues in metazoan organisms and mutations in these pathways are the cause of various forms of human cancer and developmental disorders.
Abstract: The transforming growth factor beta (TGF-beta) family of growth factors control the development and homeostasis of most tissues in metazoan organisms. Work over the past few years has led to the elucidation of a TGF-beta signal transduction network. This network involves receptor serine/threonine kinases at the cell surface and their substrates, the SMAD proteins, which move into the nucleus, where they activate target gene transcription in association with DNA-binding partners. Distinct repertoires of receptors, SMAD proteins, and DNA-binding partners seemingly underlie, in a cell-specific manner, the multifunctional nature of TGF-beta and related factors. Mutations in these pathways are the cause of various forms of human cancer and developmental disorders.
7,710 citations
TL;DR: Members of the Rho family of small guanosine triphosphatases have emerged as key regulators of the actin cytoskeleton, and through their interaction with multiple target proteins, they ensure coordinated control of other cellular activities such as gene transcription and adhesion.
Abstract: The actin cytoskeleton mediates a variety of essential biological functions in all eukaryotic cells. In addition to providing a structural framework around which cell shape and polarity are defined, its dynamic properties provide the driving force for cells to move and to divide. Understanding the biochemical mechanisms that control the organization of actin is thus a major goal of contemporary cell biology, with implications for health and disease. Members of the Rho family of small guanosine triphosphatases have emerged as key regulators of the actin cytoskeleton, and furthermore, through their interaction with multiple target proteins, they ensure coordinated control of other cellular activities such as gene transcription and adhesion.
5,969 citations
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TL;DR: Genetic alterations affecting p16INK4a and cyclin D1, proteins that govern phosphorylation of the retinoblastoma protein and control exit from the G1 phase of the cell cycle, are so frequent in human cancers that inactivation of this pathway may well be necessary for tumor development.
Abstract: Uncontrolled cell proliferation is the hallmark of cancer, and tumor cells have typically acquired damage to genes that directly regulate their cell cycles. Genetic alterations affecting p16(INK4a) and cyclin D1, proteins that govern phosphorylation of the retinoblastoma protein (RB) and control exit from the G1 phase of the cell cycle, are so frequent in human cancers that inactivation of this pathway may well be necessary for tumor development. Like the tumor suppressor protein p53, components of this "RB pathway," although not essential for the cell cycle per se, may participate in checkpoint functions that regulate homeostatic tissue renewal throughout life.
5,509 citations