1,721,040 research outputs found
ANALYSIS OF MUTANT FORMS OF THE C-SRC GENE-PRODUCT CONTAINING A PHENYLALANINE SUBSTITUTION FOR TYROSINE-416
No full textSeveral lines of evidence suggest that phosphorylation of tyrosine residue 416 (Tyr416) has a positive regulatory influence on the functional activity of the protein tyrosine kinase pp60(c-src). To further examine the functional importance of phosphorylation at Tyr416, we have eliminated this phosphoacceptor site in four functionally unique mutant forms of the c-src gene product that are phosphorylated on Tyr416 in vivo. Substitution of phenylaalnine for Tyr416 suppressed the biological activity of all of the mutant proteins as assayed by colony formation in soft agar and the induction of morphological alterations. However, the extent of this effect, and the degree to which the substitution affected the phosphorylation ofsubstrates in vivo and in vitro, varied considerably in each of the mutants. These results support the notion that phosphorylation of Tyr416 has a positive regulatory effect on the biological activity of c-src; however, this effect does not directly correlate with a general effect on the total level of tyrosine kinase activity in vitro or the level of tyrosine phosphorylation of cellular proteins in vivo
Solid tumours show osteotropism: Mechanisms of bone metastases
No full textBone metastases are a dismal consequence of cancer, causing severe morbidity and reducing the quality of life of patients. Solid tumours such as breast, prostate, lung and kidney cancer showed a marked osteotropism dependent on the special microenvironment provided by bone. Different cellular types are involved in the formation of bone metastases, indeed bone, immune system and tumour cells interact leading to bone lesions. During the bone resorption process, there is an intense cross-talk between immune system cells and osteoclasts (OCs). In particular, T cells release factors and cytokines, which rule osteoclastogenesis, and on the other hand, OCs produce factors that act on T cells, which are mediators of the tumour growth in bone. This review will summarize the main mechanisms of action in cancer-induced bone disease with particular regard to the cross-talk among cells of bone, tumour and immune system, focusing on factors and cytokines released by osteoclast, osteoblast, tumour cells and T cells. © 2013 Springer Science+Business Media New York
THE 27 KD PROTEIN ENCODED BY THE HIV NEF GENE SHARES STRUCTURAL AND FUNCTIONAL HOMOLOGIES WITH SEVERAL ONCOGENE PRODUCTS
No full textThe HIV genome contains nine coding regions, whose function in viral replication is still partially unknown. One of these, nef (Negative factor, previously called 3'-orf or orf-B), encodes a 27 kilodalton protein (p27nef) inducing an early specific immune response in infected patients. p27nef resembles an oncogene product: (a) it is myristylated on the aminoterminal glycine and is therefore associated to the cell membrane; (b) it shares homologies with pp60src, with EGF receptor and with G protein GTP binding domain; (c) it is phosphorylated on serine and threonine residues in vivo; (d) it has a GTPase activity, and (e) it is autophosphorylated on a serine residue in vitro. The role of p27nef during viral replication is still controversial; his negative role on HIV growth has been recently debated. In this paper we analyse the primary structure of p27nef and its functional properties. Strong homologies with the proteins encoded by src, erb-B-1 and ras oncogenes suggest its possible interference with the transmembrane transduction of extracellular signalling
MONOCLONAL-ANTIBODIES AGAINST CELL-SURFACE ANTIGENS OF ROUS-SARCOMA VIRUS-TRANSFORMED FIBROBLASTS
No full textIMMUNOLOGICAL DETECTION OF PROTEINS PHOSPHORYLATED AT TYROSINE IN CELLS STIMULATED BY GROWTH-FACTORS OR TRANSFORMED BY RETROVIRAL-ONCOGENE-CODED TYROSINE KINASES
No full textThe receptors for polypeptide growth factors and proteins coded by oncogenes of the src family are endowed with protein kinase activity and share the uncommon property of autophosphorylating at tyrosine residues. It is unclear whether the tyrosine kinase activity is also directed towards other targets of physiological significance. In this work, phosphotyrosine antibodies were used to detect, by Western blots and immunoprecipitation, proteins phosphorylated at tyrosine in fibroblasts either stimulated by growth factors (PDGF and EGF) or transformed by oncogene-coded tyrosine kinases. In stimulated cells the antibodies detected the autophosphorylated receptors, but only trace amounts of other proteins phosophorylated at tyrosine. In fibroblasts transformed by retroviral oncogenes (v-src, v-abl, v-fps or v-fes) proteins other than the corresponding oncogene-coded kinase, were found. A p70 was found to be heavily phosphorylated in fibroblasts transformed by v-src, v-fes and v-fps. A p130 and a p36 were found in cells transformed by v-src and v-abl. A unique p70 was phosphorylated in v-abl-transformed fibroblasts. These proteins were also phosphorylated in vitro in an immunocomplex kinase reaction. This reaction was blocked by the specific kinase inhibitors. These data strongly suggest that tyrosine kinases phosphorylate protein targets other than themselves. These targets are barely detectable in normal cells stimulated by growth factors, where the kinase activity is triggered rapidly and transiently. By contrast, a number of intracellular proteins phosphorylated at tyrosine accumulate in cells transformed by v-onc-coded kinases, endowed with constitutive and non-regulated enzymatic activity
Distal ulnar tumours - Results of management by en bloc resection in nine patients and review of the literature
No full textA variety of reconstructive procedures have been suggested for stabilizing the ulnar shaft following resection of the distal ulna for tumour. We present the results of a series of nine distal ulnar tumour resections in which four different stabilization techniques were employed, We based our results on an evaluation of function, pain, motion, strength and instability, We obtained good or excellent results in seven patients treated with a soft tissue stabilization of the ulnar stump. One patient did not undergo any stabilization procedure and scored fair in our system. A further patient who required a radiocarpal arthrodesis also had an inferior result. These results suggest that soft tissue stabilization of the ulnar stump should be performed whenever possible
'OSTEO-ONCOLOGY MULTIDISCIPLINARY CARE GROUP': A NOVEL APPROACH TO THE METASTATIC AND PRIMARY BONE TUMOR PATIENT. THE MOLINETTE EXPERIENCE
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