A cDNA Clone for Cytotactin Contains Sequences Similar to Epidermal Growth Factor-Like Repeats and Segments of Fibronectin and Fibrinogen

• Published in: Proceedings of the National Academy of Sciences - PNAS 1988-04, Vol.85 (7), p.2186-2190
• Main Authors: Jones, Frederick S., Burgoon, Mark P., Hoffman, Stanley, Crossin, Kathryn L., Cunningham, Bruce A., Edelman, Gerald M.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino acids; Animals; Antibodies; Base Sequence; Biological and medical sciences; Biotechnology; Chick Embryo; Complementary DNA; DNA; DNA - genetics; Epidermal Growth Factor - genetics; Fibrinogen - genetics; Fibronectins - genetics; Fundamental and applied biological sciences. Psychology; Gels; Genetic engineering; Genetic technics; Gizzard; Glycoproteins - genetics; Liver; Messenger RNA; Methods. Procedures. Technologies; Molecular cloning; Molecular Sequence Data; Molecules; RNA; Sequence Homology, Nucleic Acid; Tenascin
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.85.7.2186

Cytotactin is an extracellular glycoprotein that influences neuron-glia interactions. It has been shown to appear in multiple forms that are differentially expressed in neural and non-neural tissues during vertebrate development. We report here the isolation and characterization of a cytotactin cDNA clone (λ C801) that encodes 933 amino acids, equivalent to about half of a cytotactin polypeptide. Clone λ C801 is an authentic cytotactin cDNA: it encodes a polypeptide that reacts with a monoclonal anti-cytotactin antibody and its deduced amino acid sequence is identical for 15 amino acids to the directly determined sequence of a CNBr fragment that reacted with the same antibody. Southern blot analyses with fragments of λ C801 suggested that there may be only one cytotactin gene, but RNA transfer blots detected multiple mRNAs ranging in size from 6.5 to 8.0 kilobases. An 8.0-kilobase message and a Mr 240,000 cytotactin polypeptide were present in embryonic gizzard but not brain, while a 7.2-kilobase message and a Mr 220,000 polypeptide were present in brain but not gizzard. These results indicate that differential splicing of primary transcripts of the cytotactin gene yields various site-specific polypeptides. Sequence analyses of λ C801 indicated that it specifies a region with extensive similarities to other proteins: the sequence begins with four consecutive epidermal growth factor-like repeats that are followed by eight segments that closely resemble each other and the type III repeats in fibronectin, and it ends with a 66 amino acid sequence similar to part of the β and γ chains of fibrinogen. One fibronectinlike repeat contains a single Arg-Gly-Asp sequence. The similarities with all three of these apparently unrelated proteins are extensive, suggesting that cytotactin has an evolutionary and possibly a functional relationship to each.