Developmental expression of four novel serine/threonine kinase receptors homologous to the activin/transforming growth factor-beta type II receptor family.
Serine/threonine kinase transmembrane proteins are a new family of growth factor signal transducers that includes several isoforms of the activin type II receptor and the type II receptor for transforming growth factor-beta. In an effort to clone the receptor for Mullerian inhibiting substance, a member of the transforming growth factor-beta superfamily, oligonucleotide primers designed from conserved regions of these receptors' kinase domains were used for PCR amplification of fetal rat urogenital ridge cDNA. We isolated four novel receptors in this manner (designated R1-R4), each of which has structural features of the previously cloned kinases, including a small extracellular ligand-binding domain, a single hydrophobic transmembrane domain, and an intracellular serine/threonine kinase domain. In addition, each has characteristic kinase subdomains and conserved serine/threonine kinase sequences found in this family. Northern analysis revealed mRNA expression of R1-R4 in several tissues, including fetal urogenital ridge, testis, and ovary, as well as brain and lung. In situ hybridization further localized R1 to mesenchyme of the 14.5 to 15-day fetal rat Mullerian duct and to oocytes of preantral and antral follicles, sites that are consistent with the predicted localization of Mullerian inhibiting substance receptor. In addition, R2 localized specifically to seminiferous tubules of the postnatal testis. These newest members of the activin and transforming growth factor-beta type II receptor family should help define the molecular mechanisms by which this ligand superfamily affects cell growth and differentiation via membrane phosphorylation.
Pediatric Surgical Research Laboratory, Massachusetts General Hospital, Boston 02114.
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Gustafson
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Hirobe
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Donahoe
D029404:Activin Receptors; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D001921:Brain / Q000196:embryology / Q000648:ultrastructure; D001923:Brain Chemistry; D004247:DNA / Q000032:analysis / Q000235:genetics; D005260:Female; D005333:Fetus / Q000737:chemistry / Q000648:ultrastructure; D005786:Gene Expression Regulation / Q000235:genetics*; D017403:In Situ Hybridization; D008168:Lung / Q000737:chemistry / Q000196:embryology / Q000648:ultrastructure; D008297:Male; D008969:Molecular Sequence Data; D010053:Ovary / Q000737:chemistry / Q000196:embryology / Q000648:ultrastructure; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000032:analysis / Q000235:genetics*; D018125:Receptors, Transforming Growth Factor beta; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology; D013737:Testis / Q000737:chemistry / Q000196:embryology / Q000648:ultrastructure
D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D004247:DNA; D017346:Protein Serine-Threonine Kinases; D029404:Activin Receptors