Biomedical subjects

Y Goldberg

Publications and source records attributed to Y Goldberg.

29 records · Page 2Linked to original sources

PubMed1996

Neurofibromatosis type 1--an update and review for the primary pediatrician.

With an incidence of 1 in 3,000, neurofibromatosis type 1 (NF1), or von Recklinghausen disease, is one of the most common genetic disorders encountered by primary care physicians. NF1 is a multisystem disease that affects more than one million people worldwide (more than 80,000 in the United States). Although most pediatricians have patients with NF1 in their practices, many affected individuals go undiagnosed as children. This article is intended to facilitate the diagnosis and management of young patients with NF1.

Adult↗

PubMed1995

[Has protein kinase CK2 a role in the intracellular mitogenic signalling?].

The protein kinase CK2 is an ubiquitous serine-threonine kinase found in all eukaryotic cells. Although well characterized on a biochemical ground, its role and regulation in the intact cell are not clearly understood. Its possible implication in the control of cell proliferation has been examined by several different approaches. (i) Immunocytochemical detection of CK2 revealed that whereas the signal was evenly distributed throughout cycle arrested cells in primary culture, it accumulates rapidly (30-90 min) in the nuclear compartment in cells stimulated to grow. (ii) CK2 biosynthesis is activated as an early response to growth factors in quiescent cells. The neo-synthesized kinase accumulates as the cells progress through the G1 phase. This growth factor-activated biosynthesis concerns in parallel the two kinase subunits. (iii) The kinase is activated in vitro by polyamines, which are increased in cells challenged by growth factors. Spermine binds to a specific domain of the beta subunit of CK2. (iv) In addition to phosphorylation CK2 forms a molecular complex with p53, a major negative regulator of the cell cycle. The complex was demonstrated in intact cells and reconstituted in vitro (Kd 70 nM) with purified components and shown to require the beta subunit and to result in the inhibition of p53 DNA-annealing activity. These observations suggest that CK2 and p53 may play a coordinated role in the cell response to mitogenic stimuli.

Animals↗

PubMed1994

Repression of AP-1-stimulated transcription by c-Ets-1.

The transcriptional activities of c-Ets-1 and v-Ets and their functional interaction with the AP-1 factor c-Jun were investigated. Several recombinant Ets proteins were produced and purified either from bacteria or from insect cells. Plasmid DNAs that contained the polyoma virus enhancer Ets/AP-1 element were used as templates for in vitro transcription assays in the presence of HeLa nuclear extract and various combinations of the Jun and Ets proteins. Under these conditions full-length c-Ets-1 on its own does not markedly influence transcription but abolishes the strong transcriptional stimulation normally elicited by Jun. This repression depends on the Ets-binding site and on specific features of c-Ets-1 structure, as both v-Ets and a natural splicing variant c-Ets-1 (delta VII) fail to inhibit Jun activity. These findings suggest that c-Ets may act both as a transcriptional repressor or activator depending on promoter context and splicing pattern.

Alternative Splicing↗

PubMed1994

Modulation of the molecular organization and activity of casein kinase 2 by naturally occurring polyamines.

Polyamines have been reported to stimulate casein kinase 2 (CK2) in vitro. We have shown that the phosphorylation of different substrates is diversely stimulated by basic effectors and that the responsiveness of CK2 activity may be influenced by the overall conformation of the protein substrate but also by a specific interaction with the enzyme itself. Our data show that native hetero tetrameric CK2 is a spermine binding protein and a spermine binding site was identified in the N-terminal region of the beta subunit of CK2. We found that recombinant CK2 undergoes a progressive polymerization in low salt conditions, giving rise to three different polymer structures. A ring-like structure formed by the association of four protomers alpha 2 beta 2 was characterized by gel filtration, sucrose density gradient analysis and electron microscopy. Polyamines like spermine, when added under conditions where the enzyme preparation contains a mixture of various oligomers, could trigger their dissociation and their interconversion in the fully active ring structure. These results suggest that in the presence of positive effectors like polyamines, CK2 adopts a ring-like structural organization which may represent the active state of this kinase.

Amino Acid Sequence↗

PubMed1993

Generation of a temperature-sensitive cSRC.

We have created retroviruses encoding a temperature-sensitive variant of the cSrc protein, and of its activated allele cSrc(Y527F). Cells expressing the activated allele harboring this mutation displayed a transformed phenotype when grown at 34 degrees, but not at 39 degrees, as quantitated by measuring the susceptibility of the cells to contact inhibition and their ability to grow anchorage-independently at the two temperatures. The level of the mutant protein in cells grown at the high temperature was slightly reduced, and the in vitro kinase activity of the protein was hypersensitive to inactivation by heat treatment: the combination of these two defects probably explains the temperature-sensitive nature of the transformed phenotype. Surprisingly, the pattern of tyrosine phosphorylated proteins differed very little between the two temperatures, suggesting that critical substrates are few and of low abundance. The introduction of the same mutation into the wild-type allele of cSrc, Y527, also rendered the protein thermolabile. These ecotropic retroviruses should prove useful in assessing the function of cSrc in mammalian cells.

Alleles↗

PubMed1993

Anderson's disease: no linkage to the apo B locus.

We describe three patients with Anderson's disease who are members of one family; the father and mother are close relatives and three of seven children show symptoms of the disease. All patients suffered from diarrhea, failure to thrive, and recurrent infections during infancy. Although these symptoms disappeared later in life, biochemical disorders (such as low plasma levels of apolipoproteins A1 and B and cholesterol, resulting in avitaminosis E, plus failure to secrete chylomicrons after a fat meal) persisted. Electron microscopy of enterocytes of one of the patients showed accumulation of lipid vacuoles with no significant aberration of the Golgi apparatus itself. It is possible, therefore, that the disease reflects a defect in chylomicron assembly. We found that low levels of apolipoprotein (apo) B48 were present in the patients' plasma. This suggests that the processing of the B100 message resulting in apo B48 functions normally. The possibility that a mutation in the apo B gene results in an abnormal apo B48 protein is very unlikely since a variable number tandem repeat (VNTR) polymorphism probe mapped to chromosome 2 failed to show correspondence of the parent alleles with the disease. These observations confirm the suggestion that Anderson's disease is not linked to the apo B locus.

Apolipoprotein B-48↗

PubMed1990

Association between the PDGF receptor and members of the src family of tyrosine kinases.

We have examined the interaction between the platelet-derived growth factor (PDGF) receptor and three src family tyrosine kinases, pp60c-src, p59fyn, and pp62c-yes. The kinase activities of all three enzymes were elevated after PDGF stimulation of quiescent fibroblasts, coincident with association of the src family kinases with the PDGF receptor and other proteins. The presence of a protein of 81-85 kd in these complexes correlated with the detection of phosphatidylinositol (PI) kinase activity (previously described to associate with both the PDGF receptor and pp60c-src-middle T antigen). These results suggest that the physiological response to PDGF involves interaction of the receptor not only with serine/threonine and lipid kinases and a phospholipase, but also with other tyrosine kinases.

Amino Acid Sequence↗

PubMed1989

Thyroid hormone action and the erbA oncogene family.

In this review, we discuss the biological action and biochemical function of the v-erbA oncogene product, and the role of c-erbA proto-oncogene products as thyroid hormone receptors, as related to the molecular structure and function of the nuclear hormone receptors at large.

Animals↗

PubMed1988

Activation of protein kinase C or cAMP-dependent protein kinase increases phosphorylation of the c-erbA-encoded thyroid hormone receptor and of the v-erbA-encoded protein.

The c-erbA proto-oncogene encodes a nuclear receptor for thyroid hormone (T3), which is believed to stimulate transcription from specific target promoters upon binding to cis-acting DNA sequence elements. The v-erbA oncogene of avian erythroblastosis virus (AEV) encodes a ligand-independent version of this nuclear receptor. The v-erbA product inhibits terminal differentiation of avian erythroblasts, presumably by affecting the transcription of specific genes. We show here that the c-erbA-encoded nuclear receptor (p46c-erbA) is phosphorylated on serine residues on two distinct sites. One of these sites, defined by the limit tryptic phosphopeptide 28SSQCLVK, is retained on the v-erbA-encoded P75gag-v-erbA protein. This site is located in the amino-terminal domain of these molecules, 21 amino acids upstream of the DNA-binding region. Phosphorylation of this site in both p46c-erbA and P75gag-v-erbA is enhanced 10-fold following treatment of cells with activators of either protein kinase C or cAMP-dependent protein kinase. Since cAMP-dependent protein kinase phosphorylates both p46c-erbA and P75gag-v-erbA in vitro at the same site as that observed in vivo, at least part of the cAMP-dependent phosphorylation of erbA molecules in cells could result from direct phosphorylation by this enzyme. The possible role phosphorylation may play in the function of the erbA-encoded transcriptional factors is discussed.

Alpharetrovirus↗

PubMed1988

Differences in antibody recognition of the triiodothyronine nuclear receptor and c-erbA products.

The in vitro translated products of several c-erbA cDNAs have recently been shown to bind thyroid hormones with high affinity and have been termed thyroid hormone receptors. We have used a panel of five erbA-related antibodies to probe the relationship between c-erbA translated products and thyroid hormone receptors, as conventionally measured by 125I-T3 labeling of nuclear extracts. All five antibodies immunoprecipitated the chick c-erbA translated products, but only one of them recognized chick liver and brain T3 receptor, as judged by acceleration of sedimentation through sucrose gradients. None of the antibodies reacted with rat liver and brain or human liver T3 receptors, although one antibody did immunoprecipitate a human c-erbA translated product. We conclude that the T3 receptor, as conventionally measured from these sources, is related but not identical to recently cloned c-erbA sequences.

Animals↗

PubMedDate not supplied

The c-erb-A protein is a high-affinity receptor for thyroid hormone.

Hormone binding and localization of the c-erb-A protein suggest that it is a receptor for thyroid hormone, a nuclear protein that binds to DNA and activates transcription. In contrast, the product of the viral oncogene v-erb-A is defective in binding the hormone but is still located in the nucleus.

Amino Acid Sequence↗