DEVELOPMENTAL EXPRESSION OF 4 NOVEL SERINE THREONINE KINASE RECEPTORSHOMOLOGOUS TO THE ACTIVIN TRANSFORMING GROWTH-FACTOR-BETA TYPE-II RECEPTOR FAMILY

Serine/threonine kinase transmembrane proteins are a new family of gro wth factor signal transducers that includes several isoforms of the ac tivin type II receptor and the type II receptor for transforming growt h factor-beta. In an effort to clone the receptor for Mullerian inhibi ting substance, a member of the transforming growth factor-beta superf amily, oligonucleotide primers designed from conserved regions of thes e receptors' kinase domains were used for PCR amplification of fetal r at urogenital ridge cDNA. We isolated four novel receptors in this man ner (designated R1-R4), each of which has structural features of the p reviously cloned kinases, including a small extracellular ligand-bindi ng domain, a single hydrophobic transmembrane domain, and an intracell ular serine/threonine kinase domain. In addition, each has characteris tic 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 locali zed R1 to mesenchyme of the 14.5 to 15-day fetal rat Mullerian duct an d to oocytes of preantral and antral follicles, sites that are consist ent with the predicted localization of Mullerian inhibiting substance receptor. In addition, R2 localized specifically to seminiferous tubul es of the postnatal testis. These newest members of the activin and tr ansforming growth factor-beta type II receptor family should help defi ne the molecular mechanisms by which this ligand superfamily affects c ell growth and differentiation via membrane phosphorylation. (C) 1993 Wiley-Liss, Inc.