erbB-3 nucleic acids
    1.
    发明授权
    erbB-3 nucleic acids 有权
    erbB-3核酸

    公开(公告)号:US06639060B1

    公开(公告)日:2003-10-28

    申请号:US09170699

    申请日:1998-10-13

    IPC分类号: C12N1511

    摘要: A DNA fragment distinct from the epidermal growth factor receptor (EGFR) and erbB-2 genes was detected by reduced stringency hybridization of v-erbB to normal genomic human DNA. Characterization of the cloned DNA fragment mapped the region of v-erbB homology to three exons with closest homology of 64% and 67% to a contiguous region within the tyrosine kinase domains of the EGFR and erbB-2 proteins, respectively. cDNA cloning revealed a predicted 148 kd transmembrane polypeptide with structural features identifying it as a member of the erbB family, prompting designation of the new gene as erbB-3. It was mapped to human chromosome 12q11-13 and was shown to be expressed as a 6.2 kb transcript in a variety of normal tissues of epithelial origin. Markedly elevated erbB-3 mRNA levels were demonstrated in certain human mammary tumor cell lines. These findings indicate that increased erbB-3 expression, as in the case of EGFR and erbB-2, plays a role in some human malignancies. Using erbB-3 specific antibodies (polyclonal or monoclonal), the erbB-3 protein was identified as a 180 kDa glycoprotein, gp180erbB-3.

    摘要翻译: 通过v-erbB与正常基因组人DNA的严格杂交进行检测,检测出与表皮生长因子受体(EGFR)和erbB-2基因不同的DNA片段。 克隆的DNA片段的表征将v-erbB同源性的区域分别与EGFR和erbB-2蛋白的酪氨酸激酶结构域内的连续区域分别具有64%和67%最近同源性的3个外显子。 cDNA克隆揭示了具有结构特征的预测的148kd跨膜多肽,其将其识别为erbB家族的成员,促使将新基因命名为erbB-3。 它被映射到人染色体12q11-13,并且显示在上皮起源的多种正常组织中表达为6.2kb转录物。 在某些人类乳腺肿瘤细胞系中证明了显着升高的erbB-3 mRNA水平。 这些发现表明,如EGFR和erbB-2的情况,erbB-3表达的增加在一些人类恶性肿瘤中起作用。 使用erbB-3特异性抗体(多克隆或单克隆),将erbB-3蛋白鉴定为180kDa糖蛋白gp180

    Method of targeting a therapeutic agent to cells expressing the erb B-3
receptor
    3.
    发明授权
    Method of targeting a therapeutic agent to cells expressing the erb B-3 receptor 失效
    将治疗剂靶向表达erb B-3受体的细胞的方法

    公开(公告)号:US5820859A

    公开(公告)日:1998-10-13

    申请号:US473119

    申请日:1995-06-07

    摘要: A DNA fragment distinct from the epidermal growth factor receptor (EGFR) and erbB-2 genes was detected by reduced stringency hybridization of v-erbB to normal genomic human DNA. cDNA cloning revealed a predicted 148 kd transmembrane polypeptide with structural features identifying it as a member of the erbB family, prompting designation of the new gene as erbB-3. It was mapped to human chromosome 12q11-13 and was shown to be expressed as a 6.2 kb transcript in a variety of normal tissues of epithelial origin. Markedly elevated erbB-3 mRNA levels were demonstrated in certain human mammary tumor cell lines. These findings indicate that increased erbB-3 expression, as in the case of EGFR and erbB-2, plays a role in some human malignancies. Using erbB-3 specific antibodies (polyclonal or monoclonal), the erbB-3 protein was identified as a 180 kDa glycoprotein, gp180.sup.erbB-3. The intrinsic catalytic function of gp180.sup.erbB-3 was uncovered by its ability to autophosphorylate in vitro. Ligand-dependent signaling of its cytoplasmic domain was established employing transfectants which express a chimeric EGFR/erbB-3 protein, gp180.sup.EGFR/erbB-3. EGF induced tyrosine phosphorylation of the chimera and promoted soft agar colony formation of such transfectants. These findings, combined with the detection of constitutive tyrosine phosphorylation of gp180.sup.erbB-3 in 4 out of 12 human mammary tumor cell lines, implicate the activated erbB-3 product in the pathogenesis of some human malignancies. Thus, this invention also relates to procedures for targeting a therapeutic drug to cells having a high level of the receptor protein.

    摘要翻译: 通过v-erbB与正常基因组人DNA的严格杂交进行检测,检测出与表皮生长因子受体(EGFR)和erbB-2基因不同的DNA片段。 cDNA克隆揭示了具有结构特征的预测的148kd跨膜多肽,其将其识别为erbB家族的成员,促使将新基因命名为erbB-3。 它被映射到人染色体12q11-13,并且显示在上皮起源的多种正常组织中表达为6.2kb转录物。 在某些人类乳腺肿瘤细胞系中证明了显着升高的erbB-3 mRNA水平。 这些发现表明,如EGFR和erbB-2的情况,erbB-3表达的增加在一些人类恶性肿瘤中起作用。 使用erbB-3特异性抗体(多克隆或单克隆),将erbB-3蛋白鉴定为180 kDa糖蛋白gp180erbB-3。 gp180erbB-3的内在催化功能被其体外自磷酸化的能力所揭示。 使用表达嵌合EGFR / erbB-3蛋白gp180EGFR / erbB-3的转染子建立其细胞质结构域的配体依赖性信号传导。 EGF诱导嵌合体的酪氨酸磷酸化并促进这种转染子的软琼脂集落形成。 这些发现结合在12个人类乳腺肿瘤细胞系中的4个中检测到gp180erbB-3的组成型酪氨酸磷酸化,这意味着活化的erbB-3产物在一些人类恶性肿瘤的发病机制中。 因此,本发明还涉及将治疗药物靶向具有高水平受体蛋白质的细胞的方法。

    DNA segment encoding a gene for a receptor related to the epidermal
growth factor receptor
    5.
    发明授权
    DNA segment encoding a gene for a receptor related to the epidermal growth factor receptor 失效
    编码与受体相关的受体的基因的DNA段编码与生长因子受体相关

    公开(公告)号:US5183884A

    公开(公告)日:1993-02-02

    申请号:US444406

    申请日:1989-12-01

    摘要: A DNA fragment distinct from the epidermal growth factor receptor (EGF-R) and erbB-2 genes was detected by reduced stringency hybridization of v-erbB to normal genomic human DNA. Characterization of the cloned DNA fragment mapped the region of v-erbB homology to three exons with closest homology of 64% and 67% to a contiguous region within the tyrosine kinase domains of the EGF-R and erbB-2 proteins, respectively. cDNA cloning revealed a predicted 148 kd transmembrane polypeptide with structural features identifying it as a member of the erbB family, prompting designation of the new gene as erbB-3. It was mapped to human chromosome 12q11-13 and was shown to be expressed as a 6.2 kb transcript in a variety of normal tissues of epithelial origin. Markedly elevated erbB-3 mRNA levels were demonstrated in certain human mammary tumor cell lines. These findings indicate that increased erbB-3 expression, as in the case of EGF-R and erbB-2, plays a role in some human malignancies.

    摘要翻译: 通过将v-erbB与正常的基因组DNA进行严格的杂交,检测出与表皮生长因子受体(EGF-R)和erbB-2基因不同的DNA片段。 克隆的DNA片段的表征将v-erbB同源性的区域分别与EGF-R和erbB-2蛋白的酪氨酸激酶结构域内的连续区域分别具有64%和67%最接近的同源性的3个外显子。 cDNA克隆揭示了具有结构特征的预测的148kd跨膜多肽,其将其识别为erbB家族的成员,促使将新基因命名为erbB-3。 它被映射到人染色体12q11-13,并且显示在上皮起源的多种正常组织中表达为6.2kb转录物。 在某些人类乳腺肿瘤细胞系中证明了显着升高的erbB-3 mRNA水平。 这些发现表明,如EGF-R和erbB-2的情况,erbB-3表达的增加在一些人类恶性肿瘤中起作用。

    Methods of characterizing ligands for the erbB-3 receptor, methods of
influencing erbB-3 activities and methods of diagnosing erbB-3-related
neoplasm
    6.
    发明授权
    Methods of characterizing ligands for the erbB-3 receptor, methods of influencing erbB-3 activities and methods of diagnosing erbB-3-related neoplasm 失效
    表征erbB-3受体配体的方法,影响erbB-3活性的方法和诊断erbB-3相关肿瘤的方法

    公开(公告)号:US5916755A

    公开(公告)日:1999-06-29

    申请号:US475352

    申请日:1995-06-07

    摘要: A DNA fragment distinct from the epidermal growth factor receptor (EGFR) and erbB-2 genes was detected by reduced stringency hybridization of v-erbB to normal genomic human DNA. cDNA cloning revealed a predicted 148 kd transmembrane polypeptide with structural features identifying it as a member of the erbB family, prompting designation of the new gene as erbB-3. It was shown to be expressed as a 6.2 kb transcript in a variety of normal tissues of epithelial origin. Markedly elevated erbB-3 mRNA levels were demonstrated in certain human mammary tumor cell lines. These findings indicate that increased erbB-3 expression, as in the case of EGFR and erbB-2, plays a role in some human malignancies. Using erbB-3 specific antibodies (polyclonal or monoclonal), the erbB-3 protein was identified as a 180 kDa glycoprotein, gp180.sup.erbB-3. The intrinsic catalytic function of gp180.sup.erbB-3 was uncovered by its ability to autophosphorylate in vitro. These findings, combined with the detection of constitutive tyrosine phosphorylation of gp180.sup.erbB-3 in 4 out of 12 human mammary tumor cell lines, implicate the activated erbB-3 product in the pathogenesis of some human malignancies. Thus, this invention also relates to a method for detecting a receptor ligand capable of either activating or down-regulating the receptor protein, as well as procedures for purifying the resultant ligand; and a method of screening potential ligand analogs for their ability to activate the receptor protein.

    摘要翻译: 通过v-erbB与正常基因组人DNA的严格杂交进行检测,检测出与表皮生长因子受体(EGFR)和erbB-2基因不同的DNA片段。 cDNA克隆揭示了具有结构特征的预测的148kd跨膜多肽,其将其识别为erbB家族的成员,促使将新基因命名为erbB-3。 显示在上皮来源的各种正常组织中表达为6.2kb转录物。 在某些人类乳腺肿瘤细胞系中证明了显着升高的erbB-3 mRNA水平。 这些发现表明,如EGFR和erbB-2的情况,erbB-3表达的增加在一些人类恶性肿瘤中起作用。 使用erbB-3特异性抗体(多克隆或单克隆),将erbB-3蛋白鉴定为180 kDa糖蛋白gp180erbB-3。 gp180erbB-3的内在催化功能被其体外自磷酸化的能力所揭示。 这些发现结合在12个人类乳腺肿瘤细胞系中的4个中检测到gp180erbB-3的组成型酪氨酸磷酸化,这意味着活化的erbB-3产物在一些人类恶性肿瘤的发病机制中。 因此,本发明还涉及一种检测能够激活或下调受体蛋白的受体配体的方法,以及纯化所得配体的方法。 以及筛选潜在的配体类似物以激活受体蛋白的能力的方法。

    Isolated polypeptide erbB-3, related to the epidermal growth factor
receptor and antibody thereto
    9.
    发明授权
    Isolated polypeptide erbB-3, related to the epidermal growth factor receptor and antibody thereto 失效
    与表皮生长因子受体及其抗体相关的分离的多肽erbB-3

    公开(公告)号:US5480968A

    公开(公告)日:1996-01-02

    申请号:US978895

    申请日:1992-11-10

    摘要: A DNA fragment distinct from the epidermal growth factor receptor (EGFR) and erbB-2 genes was detected by reduced stringency hybridization of v-erbB to normal genomic human DNA. Characterization of the cloned DNA fragment mapped the region of v-erbB homology to three exons with closest homology of 64% and 67% to a contiguous region within the tyrosine kinase domains of the EGFR and erbB-2 proteins, respectively. cDNA cloning revealed a predicted 148 kd transmembrane polypeptide with structural features identifying it as a member of the erbB family, prompting designation of the new gene as erbB-3. It was mapped to human chromosome 12 ql 11-13 and was shown to be expressed as a 6.2 kb transcript in a variety of normal tissues of epithelial origin. Markedly elevated erbB-3 mRNA levels were demonstrated in certain human mammary tumor cell lines. These findings indicate that increased erbB-3 expression, as in the case of EGFR and erbB-2, plays a role in some human malignancies. Using erbB-3 specific antibodies (polyclonal or monoclonal), the erbB-3 protein was identified as a 180 kDa glycoprotein, gp180.sup.EGFR/erbB-3. The intrinsic catalytic function of gp180.sup.erbB-3 was uncovered by its ability to autophosphorylate in vitro. Ligand-dependent signaling of its cytoplasmic domain was established employing transfectants which express a chimeric EGFR/erbB-3 protein, gp180.sup.EGFR/erbB-3. EGF induced tyrosine phosphorylation of the chimera and promoted soft agar colony formation of such transfectants. These findings, combined with the detection of constitutive tyrosine phosphorylation of gp180.sup.erbB-3 in 4 out of 12 human mammary tumor cell lines, implicate the activated erbB-3 product in the pathogenesis of some human malignancies.

    摘要翻译: 通过v-erbB与正常基因组人DNA的严格杂交进行检测,检测出与表皮生长因子受体(EGFR)和erbB-2基因不同的DNA片段。 克隆的DNA片段的表征将v-erbB同源性的区域分别与EGFR和erbB-2蛋白的酪氨酸激酶结构域内的连续区域分别具有64%和67%最近同源性的3个外显子。 cDNA克隆揭示了具有结构特征的预测的148kd跨膜多肽,其将其识别为erbB家族的成员,促使将新基因命名为erbB-3。 它被映射到人染色体12q1111-13,并且显示在上皮起源的多种正常组织中表达为6.2kb转录物。 在某些人类乳腺肿瘤细胞系中证明了显着升高的erbB-3 mRNA水平。 这些发现表明,如EGFR和erbB-2的情况,erbB-3表达的增加在一些人类恶性肿瘤中起作用。 使用erbB-3特异性抗体(多克隆或单克隆),将erbB-3蛋白鉴定为180kDa糖蛋白gp180EGFR / erbB-3。 gp180erbB-3的内在催化功能被其体外自磷酸化的能力所揭示。 使用表达嵌合EGFR / erbB-3蛋白gp180EGFR / erbB-3的转染子建立其细胞质结构域的配体依赖性信号传导。 EGF诱导嵌合体的酪氨酸磷酸化并促进这种转染子的软琼脂集落形成。 这些发现结合在12个人类乳腺肿瘤细胞系中的4个中检测到gp180erbB-3的组成型酪氨酸磷酸化,这意味着活化的erbB-3产物在一些人类恶性肿瘤的发病机制中。