[
    {
        "id": "thesis:6670",
        "collection": "thesis",
        "collection_id": "6670",
        "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:09142011-114200593",
        "primary_object_url": {
            "basename": "Aroian_rv_1992.pdf",
            "content": "final",
            "filesize": 34350162,
            "license": "other",
            "mime_type": "application/pdf",
            "url": "/6670/1/Aroian_rv_1992.pdf",
            "version": "v4.0.0"
        },
        "type": "thesis",
        "title": "The let-23 gene of the nematode C. elegans : genetics and molecular biology of a member of the EGF receptor tyrosine kinase family",
        "author": [
            {
                "family_name": "Aroian",
                "given_name": "Raffi V",
                "clpid": "Aroian-R-V"
            }
        ],
        "thesis_advisor": [
            {
                "family_name": "Sternberg",
                "given_name": "Paul W.",
                "clpid": "Sternberg-P-W"
            }
        ],
        "thesis_committee": [
            {
                "family_name": "Benzer",
                "given_name": "Seymour",
                "clpid": "Benzer-S"
            },
            {
                "family_name": "Davidson",
                "given_name": "Eric H.",
                "clpid": "Davidson-E-H"
            },
            {
                "family_name": "Emr",
                "given_name": "Scott D.",
                "clpid": "Emr-S-D"
            },
            {
                "family_name": "Lipshitz",
                "given_name": "Howard D.",
                "clpid": "Lipshitz-H-D"
            }
        ],
        "local_group": [
            {
                "literal": "div_biol"
            }
        ],
        "abstract": "<p>Genetic studies indicate that the let-23 gene affects several developmental decisions in the nematode\r\nCaenorhabditis elegans. let-23 is required for the proper development of the hermaphrodite vulva, the male tail, and the posterior ectoderm. In addition, let-23 mutations can cause lethality and hermaphrodite sterility. These five let-23 functions can be independently mutated, suggesting that the let-23 protein encodes tissuespecific functions . Furthermore, let-23 controls two opposing pathways: one that stimulates and another that inhibits vulval\r\ndevelopment. These two pathways ensure that the proper level of vulval development occurs. Twenty let-23 alleles exist: 14 eliminate function (null), three reduce function in all tissues (hypomorphic), and three reduce function in certain tissues (tissue-specific). In addition, two of these alleles are defective in the inhibitory vulval pathway.</p>\r\n\r\n<p>The let-23 primary structure resembles that of the mammalian epidermal growth factor receptor (EGFR). The let-23 protein possesses putative ligand binding,\r\ntransmembrane, and tyrosine kinase domains, as well as cysteine-rich regions, all with the characteristics of the EGFR family. Like let-23, mammalian EGFR is multifunctional, encodes tissuespecific functions, and functions in stimulatory and inhibitory pathways. let-23 may be the receptor in the vulva for the anchor-cell\r\ninductive signal. Furthermore, genetic data indicate let-23 acts upstream of the let-60 ras gene, supporting mammalian studies that suggest a link between EGFR and ras.</p>\r\n\r\n<p>To investigate how EGFR primary structure relates to function, mutations in eight let-23 alleles have been\r\nsequenced. Five null alleles alter sequences in both the kinase and the extracellular domains. These alterations suggest that let-23 has kinase activity and that the extra cysteine domain found only in invertebrate EGFRs is important. A strong hypomorphic allele mutates one of the conserved extracellular cysteines close to the ligand binding domain. A tissue-specific allele mutates an\r\nintronlexon boundary in the C-terminus. This mutation suggests that the C-terminus can provide tissue-specific information. Finally, a hypomorphic allele that is defective in the let\u202223 inhibitory vulval pathway alters a different intron/exon boundary in the C-terminus. This mutation results in numerous, unexpected transcripts. Models are suggested to account for the behavior of this allele.</p>\r\n",
        "doi": "10.7907/q10c-b807",
        "publication_date": "1992",
        "thesis_type": "phd",
        "thesis_year": "1992"
    }
]