Orientation of the v-erb-B gene product in the plasma membrane.

Schatzman, Randall C.; Evan, Gérard I.; Privalsky, Martin L.; Bishop, J. Michael

doi:10.1128/mcb.6.4.1329

Cited by 32 publications

(17 citation statements)

References 27 publications

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“…The products of most other known oncogenes are localized to the cytoplasm, to the membrane, or to both subcellular components. Oncogenes encoding growth factors, such as sis (20,33), or growth factor receptors, including erbB (34,35) andfms (36,37), are synthesized in association with the endoplasmic reticulum and become associated with peripheral cell membranes where they are exposed to the cell surface. Preliminary immunofluorescence evidence indicates that dbl antigenic determinants are not exposed on the cell surface (L. Varesio, personal communication), although analysis of a broader range of antisera will be required to exclude this possibility rigorously.…”

Section: Discussionmentioning

confidence: 99%

Identification of the protein encoded by the human diffuse B-cell lymphoma (dbl) oncogene.

Srivastava¹,

Wheelock²,

Aaronson³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

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The dbl oncogene was initially isolated from a human diffuse B-cell lymphoma. Antisera from mice bearing tumors induced by this oncogene specifically detected a protein of about 66 kDa (p66) in dbl transformants. dbl cDNA-selected poly(A)I RNA isolated from a transfectant clone expressing p66 directed the in vitro synthesis of this protein, establishing that it is encoded by dbl. Subcellulat localization studies revealed that p66 is a cytoplasmic protein distributed between cytosol and crude membrane fractions. Moreover, p66 was shown to be a phosphoprotein, with phosphorylation specific to serine residues. Our characterization of the dbl-encoded protein appears to distinguish this transforming gene product from those of other known oncogenes.

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Section: Discussionmentioning

confidence: 99%

Identification of the protein encoded by the human diffuse B-cell lymphoma (dbl) oncogene.

Srivastava¹,

Wheelock²,

Aaronson³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

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“…All of these mutations are believed to play a role in the activation of the protein's transforming activity (21,32,42,43). The product of v-erbB is synthesized as a 61-kDa precursor that is subsequently modified by N-linked glycosylation and phosphorylation to 65-, 68-, and 74-kDa species (3,35,37). The 65-and 68-kDa processing intermediates are associated primarily with intracellular membranes, whereas the 74-kDa form is found associated with the plasma membrane (3).…”

mentioning

confidence: 99%

The amino-terminal 14 amino acids of v-src can functionally replace the extracellular and transmembrane domains of v-erbB.

McMahon¹,

Schatzman²,

Bishop³

1991

Mol. Cell. Biol.

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The retroviral oncogene v-erbB encodes a truncated form of the receptor for epidermal growth factor, an integral membrane protein-tyrosine kinase. By contrast, the oncogene v-src encodes a protein-tyrosine kinase that is a peripheral membrane protein. The morphologies and spectra of cells transformed by these two oncogenes differ. In an effort to identify the functional determinant(s) of these differences, we constructed and tested first deletion mutants of v-erbB and then chimeras between v-src and v-erbB. As reported previously, the absence of any membrane anchorage eliminated transformation by v-erbB. Anchorage of the cytoplasmic kinase domain of v-erbB to membranes with amino-terminal portions of the v-src protein permitted transformation. The phenotype and spectrum of transformation were those expected for v-erbB rather than for v-src. The transforming chimeras lost their biological activity if the signal for myristylation at the amino terminus of v-src was compromised by mutation. Biochemical fractionations revealed a correlation between transforming activity and the association of chimeric gene products with the membrane fraction of the cell. For reasons not yet apparent, the combined presence of membrane anchorage domains of v-src and the transmembrane domain of v-erbB in the same chimera typically (but not inevitably) impeded transformation. Our results suggest that the specificity of transformation by v-erbB resides in the selection of substrates by the cytoplasmic domain of the gene product. The protein retains access to those substrates even when anchored to the membrane in the manner of a peripheral rather than a transmembrane protein.

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“…PROCESSING OF NB TO CONTAIN POLYLACTOSAMINOGLYCANS liver B-chain low-density lipoprotein, ovalbumin, immunoglobulins, band 3, glycophorin A, HA of the WSN strain of influenza virus, avian erythroblastosis virus erbB, and simian sarcoma virus v-sis [1,20,23,25,28,41,[45][46][47]51]). …”

mentioning

confidence: 99%

Polylactosaminoglycan modification of a small integral membrane glycoprotein, influenza B virus NB.

Williams¹,

Lamb²

1988

Mol. Cell. Biol.

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The structure of the carbohydrate components of NB, the small integral membrane glycoprotein of influenza B virus, was investigated. The carbohydrate chains of NB are processed from the high-mannose form (NB18) to a heterogeneous form of much higher molecular weight, designated NBp. Selection of this carbohydrate-containing form of NB with Datura stramonium lectin, its susceptibility to digestion by endo-beta-galactosidase, and determination of the size of NBp glycopeptides by gel filtration chromatography suggested that the increase in molecular weight is due to processing to polylactosaminoglycan. Investigation of the polypeptides produced by influenza B/Lee/40 virus infection of several cell types and another strain of influenza B virus suggested that the signal for modification to polylactosaminoglycan is contained in NB. Expression of mutants of NB lacking either one or both of the normal N-terminal sites of asparagine-linked glycosylation indicated that both carbohydrate chains are modified to contain polylactosaminoglycan. NBp and a small amount of unprocessed NB18 are expressed at the infected-cell surface, as determined by digestion of the surfaces of intact cells with various endoglycosidases. Unglycosylated NB, expressed either in influenza B virus-infected cells treated with tunicamycin or in cells expressing the NB mutant lacking both N-linked glycosylation sites, was expressed at the cell surface, indicating that NB does not require carbohydrate addition for transport.

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Orientation of the v-erb-B gene product in the plasma membrane.

Cited by 32 publications

References 27 publications

Identification of the protein encoded by the human diffuse B-cell lymphoma (dbl) oncogene.

Identification of the protein encoded by the human diffuse B-cell lymphoma (dbl) oncogene.

The amino-terminal 14 amino acids of v-src can functionally replace the extracellular and transmembrane domains of v-erbB.

Polylactosaminoglycan modification of a small integral membrane glycoprotein, influenza B virus NB.

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