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J Schlessinger

Publications and source records attributed to J Schlessinger.

405 records · Page 23Linked to original sources
PubMed1972

Circular polarization of fluorescence of probes bound to chymotrypsin. Change in asymmetric environment upon electronic excitation.

The circular polarization of fluorescence is related to the conformational asymmetry of the emitting molecule in the first singlet excited state in the same way that circular dichroism is related to the conformational asymmetry of the absorbing molecule in the electronic ground state. By measurement of these optical phenomena, the induced asymmetry of two chromophores bound to chymotrypsin (EC 3.4.4.5) when in the ground state was compared with the induced asymmetry of the ligands when in the excited state. The two chromophores studied were 2-p-toluidinylnaphthalene-6-sulfonate (TNS), bound at a specific site which is not the active site of the protein, and an anthraniloyl group, bound at the active site of the enzyme. Both chromophores showed a change in induced asymmetry upon electronic excitation, the effect being particularly large in the case of the TNS chromophore. It is thus concluded that the orientation of TNS in the binding site, its freedom of rotation in its site, the strength of binding, or even the site of binding of the dye to the protein might have changed upon electronic excitation.

Chymotrypsin↗
PubMedDate not supplied

Characterization of the detergent solubilized receptor for gastrin-releasing peptide.

Properties of detergent solubilized gastrin-releasing peptide receptor were investigated. Swiss 3T3 membranes were covalently labeled with [125I]GRP and homobifunctional cross-linkers. A major labeled protein of 75 kDa was resolved using SDS-polyacrylamide gel electrophoresis. When the same preparation was solubilized with zwitterionic detergent and analyzed under nondenaturing conditions the protein bound radioactivity was resolved in two different peaks, a major one of apparent molecular weight 220,000 (peak 1) and a minor one of 80,000 (peak 2) both containing the 75 kDa protein. Specific ligand binding activity also eluted with peak 1. These results indicate that the active form of bombesin/GRP receptor is a large complex containing the 75 kDa ligand binding domain.

Animals↗
PubMedDate not supplied

Synthetic peptide approach to the analysis of kinase activities of avian EGF receptor and v-erbB protein.

Analysis of the structure and function of a protein such as the epidermal growth factor receptor is facilitated by the use of antibodies directed against discrete portions of the protein. Here, we describe the characterization and use of antibodies directed against synthetic peptides corresponding to specific portions of the epidermal growth factor receptor and/or v-erbB protein. In particular, one useful antiserum has allowed us to compare the protein kinase activities of the epidermal growth factor receptor and the v-erbB proteins and to conclude that the v-erbB protein is a protein-tyrosine specific kinase as is its homologue the avian epidermal growth factor receptor.

Alpharetrovirus↗
PubMedDate not supplied

Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences.

Each of six peptides derived from the human epidermal growth factor (EGF) receptor very closely matches a part of the deduced sequence of the v-erb-B transforming protein of avian erythroblastosis virus (AEV). In all, the peptides contain 83 amino acid residues, 74 of which are shared with v-erb-B. The AEV progenitor may have acquired the cellular gene sequences of a truncated EGF receptor (or closely related protein) lacking the external EGF-binding domain but retaining the transmembrane domain and a domain involved in stimulating cell proliferation. Transformation of cells by AEV may result, in part, from the inappropriate acquisition of a truncated EGF receptor from the c-erb-B gene.

Amino Acid Sequence↗
PubMedDate not supplied

Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells.

The complete 1,210-amino acid sequence of the human epidermal growth factor (EGF) receptor precursor, deduced from cDNA clones derived from placental and A431 carcinoma cells, reveals close similarity between the entire predicted v-erb-B mRNA oncogene product and the receptor transmembrane and cytoplasmic domains. A single transmembrane region of 23 amino acids separates the extracellular EGF binding and cytoplasmic domains. The receptor gene is amplified and apparently rearranged in A431 cells, generating a truncated 2.8-kilobase mRNA which encodes only the extracellular EGF binding domain.

Amino Acid Sequence↗
PubMedDate not supplied

Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin.

Epidermal growth factor (EGF), through interaction with specific cell surface receptors, generates a pleiotropic response that, by a poorly defined mechanism, can induce proliferation of target cells. Subversion of the EGF mitogenic signal through expression of a truncated receptor may be involved in transformation by the avian erythroblastosis virus (AEV) oncogene v-erb-B, suggesting that similar EGF receptor defects may be found in human neoplasias. Overexpression of EGF receptors has been reported on the epidermoid carcinoma cell line A431, in various primary brain tumours and in squamous carcinomas. In A431 cells the receptor gene is amplified. Here we show that 4 of 10 primary brain tumours of glial origin which express levels of EGF receptors that are higher than normal also have amplified EGF receptor genes. Amplified receptor genes were not detected in the other brain tumours examined. Further analysis of EGF receptor defects may show that such altered expression and amplification is a particular feature of certain human tumours.

Brain Neoplasms↗
PubMedDate not supplied

A chimaeric receptor allows insulin to stimulate tyrosine kinase activity of epidermal growth factor receptor.

The cell surface receptors for insulin and epidermal growth factor (EGF) appear to share a common evolutionary origin, as suggested by structural similarity of cysteine-rich regions in their extracellular domains and a highly conserved tyrosine-specific protein kinase domain. Only minor similarity is found outside this catalytic domain, as expected for receptors that have different ligand specificities and generate different biological signals. The EGF receptor is a single polypeptide chain but the insulin receptor consists of distinct alpha and beta subunits that function as an alpha 2 beta 2 heterotetrameric receptor complex. Provoked by this major structural difference in two receptors that carry out parallel functions, we have designed a chimaeric receptor molecule comprising the extracellular portion of the insulin receptor joined to the transmembrane and intracellular domains of the EGF receptor to investigate whether one ligand will activate the tyrosine kinase domain of the receptor for the other ligand. We show here that the EGF receptor kinase domain of the chimaeric protein, expressed transiently in simian cells, is activated by insulin binding. This strongly suggests that insulin and EGF receptors employ closely related or identical mechanisms for signal transduction across the plasma membrane.

Chimera↗
PubMedDate not supplied

Interaction of epidermal growth factor with vasoactive hormones in the regulation of phospholipase A2.

The interaction of growth factors with their receptors initiates a series of intracellular events that are of critical importance in the control of normal cell proliferation. In this regard considerable attention has focused on the coupling of phospholipase C-gamma to growth factor receptor tyrosine kinases. In contrast, the interaction of growth factors with phospholipase A2 has received less attention, most likely because the arachidonic acid release response has been considered to be an accompaniment of phospholipase C activation. Work from our laboratory using a well defined model system demonstrated a distinct coupling relationship of epidermal growth factor to phospholipase A2. This review focuses on the interaction of the epidermal growth factor receptor with phospholipases involved in both mitogenic and non-mitogenic responses and discusses their possible relation with vasoactive hormones.

Angiotensin II↗