L Soussan

Publications (7)31.03 Total impact

• Source

  Available from: PubMed Central

  Article: ERG30, a VAP-33-related protein, functions in protein transport mediated by COPI vesicles.

  L Soussan, D Burakov, M P Daniels, M Toister-Achituv, A Porat, Y Yarden, Z Elazar
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  ABSTRACT: Intracellular transport of newly synthesized and mature proteins via vesicles is controlled by a large group of proteins. Here we describe a ubiquitous rat protein-endoplasmic reticulum (ER) and Golgi 30-kD protein (ERG30)-which shares structural characteristics with VAP-33, a 33-kD protein from Aplysia californica which was shown to interact with the synaptic protein VAMP. The transmembrane topology of the 30-kD ERG30 corresponds to a type II integral membrane protein, whose cytoplasmic NH(2) terminus contains a predicted coiled-coil motif. We localized ERG30 to the ER and to pre-Golgi intermediates by biochemical and immunocytochemical methods. Consistent with a role in vesicular transport, anti-ERG30 antibodies specifically inhibit intra-Golgi transport in vitro, leading to significant accumulation of COPI-coated vesicles. It appears that ERG30 functions early in the secretory pathway, probably within the Golgi and between the Golgi and the ER.
  The Journal of Cell Biology 08/1999; 146(2):301-11. · 10.26 Impact Factor
• Article: Neu differentiation factor stimulates phosphorylation and activation of the Sp1 transcription factor.

  I Alroy, L Soussan, R Seger, Y Yarden
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  ABSTRACT: Neu differentiation factors (NDFs), or neuregulins, are epidermal growth factor-like growth factors which bind to two tyrosine kinase receptors, ErbB-3 and ErbB-4. The transcription of several genes is regulated by neuregulins, including genes encoding specific subunits of the acetylcholine receptor at the neuromuscular junction. Here, we have examined the promoter of the acetylcholine receptor epsilon subunit and delineated a minimal CA-rich sequence which mediates transcriptional activation by NDF (NDF-response element [NRE]). Using gel mobility shift analysis with an NRE oligonucleotide, we detected two complexes that are induced by treatment with neuregulin and other growth factors and identified Sp1, a constitutively expressed zinc finger phosphoprotein, as a component of one of these complexes. Phosphatase treatment, two-dimensional gel electrophoresis, and an in-gel kinase assay indicated that Sp1 is phosphorylated by a 60-kDa kinase in response to NDF-induced signals. Moreover, Sp1 seems to act downstream of all members of the ErbB family and thus may funnel the signaling of the ErbB network into the nucleus.
  Molecular and Cellular Biology 04/1999; 19(3):1961-72. · 5.53 Impact Factor
• Article: Isolation and characterization of the highly phosphorylated repeat domain of distinct heavy neurofilament subunit (NF-H) isoforms.

  L Soussan, A Admon, A Aharoni, Y Cohen, D M Michaelson
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  ABSTRACT: 1. Recent examination of the hypothesis that distinctly phosphorylated NF-H isoforms exist in different types of neurons revealed that the extent of phosphorylation of the heavy neurofilament polypeptide of bovine ventral root motor neurons is markedly higher than that of dorsal root neurons. 2. In the present study we employed endoproteinase ASP-N for isolating the Lys-Ser-Pro (KSP)-rich domain of NF-H, which contains most of the NF-H phosphorylation sites. 3. Treatment of NF-H with ASP-N endoproteinase results in a cascade of products, the last of which is a polypeptide with apparent molecular weight of 120 kDa. Amino terminal sequence and amino acid composition analysis revealed that this fragment contains the KSP-rich domain of NF-H. 4. Treatment of ventral and dorsal root NF-H with ASP-N endoproteinase and analysis of the phosphoserine contents of the resulting 120 kDa fragments revealed that the 120 kDa fragment of ventral root NF-H is significantly more phosphorylated than that of dorsal root NF-H. 5. These findings show that the difference in extent of phosphorylation of ventral and dorsal root NF-H is due at least partly to the KSP-rich domain of NF-H.
  Cellular and Molecular Neurobiology 09/1996; 16(4):463-77. · 1.97 Impact Factor
• Article: Diversification of Neu differentiation factor and epidermal growth factor signaling by combinatorial receptor interactions.

  R Pinkas-Kramarski, L Soussan, H Waterman, G Levkowitz, I Alroy, L Klapper, S Lavi, R Seger, B J Ratzkin, M Sela, Y Yarden
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  ABSTRACT: The ErbB family includes two receptors, ErbB-1 and ErbB-3, that respectively bind to epidermal growth factor and Neu differentiation factor, and an orphan receptor, ErbB-2. Unlike ErbB-1 and ErbB-2, the intrinsic tyrosine kinase of ErbB-3 is catalytically impaired. By using interleukin-3-dependent cells that ectopically express the three ErbB proteins or their combinations, we found that ErbB-3 is devoid of any biological activity but both ErbB-1 and ErbB-2 can reconstitute its extremely potent mitogenic activity. Transactivation of ErbB-3 correlates with heterodimer formation and is reflected in receptor phosphorylation and the transregulation of ligand affinity. Inter-receptor interactions enable graded proliferative and survival signals: heterodimers are more potent than homodimers, and ErbB-3-containing complexes, especially the ErbB-2/ErbB-3 heterodimer, are more active than ErbB-1 complexes. Nevertheless, ErbB-1 signaling displays dominance over ErbB-3 when the two receptors are coexpressed. Although all receptor combinations activate the mitogen-activated protein kinases ERK and c-Jun kinase, they differ in their rate of endocytosis and in coupling to intervening signaling proteins. It is conceivable that combinatorial receptor interactions diversify signal transduction and confer double regulation, in cis and in trans, of the superior mitogenic activity of the kinase-defective ErbB-3.
  The EMBO Journal 06/1996; 15(10):2452-67. · 9.20 Impact Factor
• Article: Distinctly phosphorylated neurofilaments in different classes of neurons.

  L Soussan, A Barzilai, D M Michaelson
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  ABSTRACT: Recent immunohistochemical experiments revealed that specific anti-neurofilament monoclonal antibodies yield distinct patterns in different types of neurons. This led to the suggestion that neurofilaments are a family of heterogeneous molecules whose occurrence and distribution are a function of cell type. In the present study we examined the hypothesis that this heterogeneity is due to differences in the extent of phosphorylation of neurofilament proteins in distinct types of neurons. In view of the large number of potential phosphorylation sites on the heavy neurofilament protein (NF-H), we focused on this protein and examined its extent of phosphorylation in different types of neurons. This was performed using neurofilaments isolated from axons of the cholinergic bovine ventral root motor neurons and of the chemically heterogeneous bovine dorsal root neurons. Two-dimensional gel electrophoresis revealed that the isoelectric point of ventral root NF-H (pl 5.10) was approximately 0.2 pl units more acidic than that of dorsal root NH-F. This difference was abolished by treating the neurofilaments with alkaline phosphatase, suggesting that the excess negative charge of ventral root NF-H is due to increased levels of phosphorylation. Amino acid analysis confirmed that the phosphoserine content of ventral root NF-H (27.2 +/- 2.5% of the serines) is markedly higher than that of dorsal root NF-H (15.5 +/- 6.2% of the serines). These findings provide a novel system for studying the biochemistry and function of distinctly phosphorylated neurofilaments in different types of neurones.
  Journal of Neurochemistry 03/1994; 62(2):770-6. · 4.06 Impact Factor
• Article: A rapid and sensitive heterogeneous immunoelectrochemical assay using disposable electrodes.

  E Hadas, L Soussan, I Rosen-Margalit, A Farkash, J Rishpon
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  ABSTRACT: In this novel enzyme-tagged immuoelectrochemical assay, disposable carbon felt discs serve both as electrodes and as the heterogeneous solid phase. Antibodies are immobilized on the carbon felt via a diaminoalkane-biotin-avidin-biotin bridge. Alkaline phosphatase is used as a label. Bound antibodies are monitored by following the electro-oxidation of aminophenol, produced enzymatically from p-amino-phenyl phosphate by the immobilized alkaline phosphatase at the electrode surface. A model system designed for determination of mouse IgG concentration yielded a calibration curve ranging from 10 pg/ml to 100 micrograms/ml. This assay can be performed rapidly and a single determination completed within 20 minutes. The system is useful also for rapid quantitation of a small number (approximately 80 organisms per ml) of bacteria.
  Journal of immunoassay 02/1992; 13(2):231-52.
• Article: Alzheimer's disease and Down's syndrome antibodies bind to the heavy neurofilament protein of cholinergic neurons.

  K Tchernakov, L Soussan, S Hassin-Baer, E Wertman, D M Michaelson
  Research in Immunology 143(6):670-5.