Author
Michael B. Sporn
Other affiliations: Cornell University, Reata Pharmaceuticals, University of Texas MD Anderson Cancer Center ...read more
Bio: Michael B. Sporn is an academic researcher from Dartmouth College. The author has contributed to research in topics: Transforming growth factor & Transforming growth factor beta. The author has an hindex of 157, co-authored 559 publications receiving 94605 citations. Previous affiliations of Michael B. Sporn include Cornell University & Reata Pharmaceuticals.
Papers published on a yearly basis
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TL;DR: It is concluded that bone-forming cells are a source for the TGF-beta that is found in bone, and that these cells may be modulated by this factor in an autocrine fashion.
Abstract: Transforming growth factor-type beta (TGF-beta) has been identified as a constituent of bone matrix (Seyedin, S. M., A. Y. Thompson, H. Bentz, D. M. Rosen, J. M. McPherson, A. Conti, N. R. Siegel, G. R. Gallupi, and K. A. Piez, 1986, J. Biol. Chem. 261:5693-5695). We used both developing bone and bone-forming cells in vitro to demonstrate the cellular origin of this peptide. TGF-beta mRNA was detected by Northern analysis in both developing bone tissue and fetal bovine bone-forming cells using human cDNA probes. TGF-beta was shown to be synthesized and secreted by metabolically labeled bone cell cultures by immunoprecipitation from the medium. Further, TGF-beta activity was demonstrated in conditioned media from these cultures by competitive radioreceptor and growth promotion assays. Fetal bovine bone cells (FBBC) were found to have relatively few TGF-beta receptors (5,800/cell) with an extremely low Kd of 2.2 pM (high binding affinity). In contrast to its inhibitory effects on the growth of many cell types including osteosarcoma cell lines, TGF-beta stimulated the growth of subconfluent cultures of FBBC; it had little effect on the production of collagen by these cells. We conclude that bone-forming cells are a source for the TGF-beta that is found in bone, and that these cells may be modulated by this factor in an autocrine fashion.
548 citations
TL;DR: The biologically inactive form of TGF-beta, which constitutes greater than 98% of autocrine T GF-beta secreted by all of the twelve different cell types assayed, was shown to be unable to bind to the receptor without prior activation in vitro, and it is proposed that this may prevent premature interaction of Autocrine ligand and receptor in the Golgi apparatus.
Abstract: Scatchard analyses of the binding of transforming growth factor-beta (TGF-beta) to a wide variety of different cell types in culture revealed the universal presence of high affinity (Kd = 1-60 pM) receptors for TGF-beta on every cell type assayed, indicating a wide potential target range for TGF-beta action. There was a strong (r = +0.85) inverse relationship between the receptor affinity and the number of receptors expressed per cell, such that at low TGF-beta concentrations, essentially all cells bound a similar number of TGF-beta molecules per cell. The binding of TGF-beta to various cell types was not altered by many agents that affect the cellular response to TGF-beta, suggesting that modulation of TGF-beta binding to its receptor may not be a primary control mechanism in TGF-beta action. Similarly, in vitro transformation resulted in only relatively small changes in the cellular binding of TGF-beta, and for those cell types that exhibited ligand-induced down-regulation of the receptor, down-regulation was not extensive. Thus the strong conservation of binding observed between cell types is also seen within a given cell type under a variety of conditions, and receptor expression appears to be essentially constitutive. Finally, the biologically inactive form of TGF-beta, which constitutes greater than 98% of autocrine TGF-beta secreted by all of the twelve different cell types assayed, was shown to be unable to bind to the receptor without prior activation in vitro. It is proposed that this may prevent premature interaction of autocrine ligand and receptor in the Golgi apparatus.
542 citations
TL;DR: The data suggest that platelet-mediated proliferation of aortic smooth muscle cells in vivo may not result solely from the stimulatory effect of Platelet-derived growth factor (PDGF), but rather from an interaction of platelet factors which has the intrinsic ability to limit as well as stimulate mitosis.
Abstract: A specific radioimmunoassay for type beta transforming growth factor (TGF-beta) was developed and used to show that human platelets treated with thrombin release TGF-beta as a consequence of degranulation. The thrombin concentrations required to induce release of TGF-beta parallel those concentrations that release the alpha-granule marker, beta-thromboglobulin. Related studies showed that TGF-beta acts on early passage, explant cultures of bovine aortic smooth muscle cells by inhibiting the effect of mitogens on proliferation of subconfluent cell monolayers yet synergizing with mitogens to stimulate growth of the same cells when cultured in soft agar. The results show that primary cultures of bovine aortic smooth muscle cells and established normal rat kidney cells behave similarly with regard to TGF-beta action. Moreover, the data suggest that platelet-mediated proliferation of aortic smooth muscle cells in vivo may not result solely from the stimulatory effect of platelet-derived growth factor (PDGF), but rather from an interaction of platelet factors which has the intrinsic ability to limit as well as stimulate mitosis.
532 citations
TL;DR: An important role is suggested for maternal sources of TGF-beta 1 during development and, more generally, evidence for maternal rescue of targeted gene disruption in the fetus is provided.
Abstract: Maternal sources of transforming growth factor-beta 1 (TGF-beta 1) are shown here to contribute to the normal appearance and perinatal survival of TGF-beta 1 null newborn mice. Labeled TGF-beta 1 crossed the placenta and was recovered intact from various tissues after oral administration to mouse pups. TGF beta-1 protein was also detected in cells recovered from breast milk. In immunohistochemical analyses, TGF-beta 1 null embryos and null newborn pups born to TGF-beta 1 heterozygotes stained positive for TGF-beta 1, whereas those born to a null female were negative and had severe cardiac abnormalities. These results suggest an important role for maternal sources of TGF-beta 1 during development and, more generally, provide evidence for maternal rescue of targeted gene disruption in the fetus.
508 citations
TL;DR: Of all of the growth factors, none has been found to have the diversity of effects on ECM ascribed to transforming growth factor-β (TGF-β).
470 citations
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TL;DR: This work has been supported by the Department of the Army and the National Institutes of Health, and the author acknowledges the support and encouragement of the National Cancer Institute.
28,811 citations
28 Jul 2005
TL;DR: PfPMP1）与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。
18,940 citations
TL;DR: The ability to control the expression of genes encoding these molecules and to target specific cell types provides opportunities to develop new diagnostic and therapeutic agents to induce the regression of the lesions and, possibly, to prevent their formation.
Abstract: Atherosclerosis, the principal cause of heart attack, stroke and gangrene of the extremities, is responsible for 50% of all mortality in the USA, Europe and Japan. The lesions result from an excessive, inflammatory-fibroproliferative response to various forms of insult to the endothelium and smooth muscle of the artery wall. A large number of growth factors, cytokines and vasoregulatory molecules participate in this process. Our ability to control the expression of genes encoding these molecules and to target specific cell types provides opportunities to develop new diagnostic and therapeutic agents to induce the regression of the lesions and, possibly, to prevent their formation.
10,861 citations
TL;DR: The principal mechanisms that govern the effects of inflammation and immunity on tumor development are outlined and attractive new targets for cancer therapy and prevention are discussed.
8,664 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