Cloning of a type I TGF-beta receptor and its effect on TGF-beta binding to the type II receptor.

Transforming growth factor-beta (TGF-beta) affects cellular proliferation, differentiation, and interaction with the extracellular matrix primarily through interaction with the type I and type II TGF-beta receptors. The type II receptors for TGF-beta and activin contain putative serine-threonine kinase domains. A murine serine-threonine kinase receptor, Tsk 7L, was cloned that shared a conserved extracellular domain with the type II TGF-beta receptor. Overexpression of Tsk 7L alone did not increase cell surface binding of TGF-beta, but coexpression with the type II TGF-beta receptor caused TGF-beta to bind to Tsk 7L, which had the size of the type I TGF-beta receptor. Overexpression of Tsk 7L inhibited binding of TGF-beta to the type II receptor in a dominant negative fashion. Combinatorial interactions and stoichiometric ratios between the type I and II receptors may therefore determine the extent of TGF-beta binding and the resulting biological activities.

[1]  R. Derynck,et al.  Inactivation of the type II receptor reveals two receptor pathways for the diverse TGF-beta activities. , 1993, Science.

[2]  Jeffrey L. Wrana,et al.  TGFβ signals through a heteromeric protein kinase receptor complex , 1992, Cell.

[3]  K. Titani,et al.  Isolation and characterization of activin receptor from mouse embryonal carcinoma cells. Identification of its serine/threonine/tyrosine protein kinase activity. , 1992, The Journal of biological chemistry.

[4]  J. Massagué.  Receptors for the TGF-β family , 1992, Cell.

[5]  T. Soderling,et al.  Serine/threonine protein kinases , 1992, Current Opinion in Neurobiology.

[6]  L. Mathews,et al.  Cloning of a second type of activin receptor and functional characterization in Xenopus embryos. , 1992, Science.

[7]  T. Hunter,et al.  Dual-specificity protein kinases: will any hydroxyl do? , 1992, Trends in biochemical sciences.

[8]  R. Weinberg,et al.  Expression cloning of the TGF-β type II receptor, a functional transmembrane serine/threonine kinase , 1992, Cell.

[9]  J. Massagué,et al.  Novel activin receptors: Distinct genes and alternative mRNA splicing generate a repertoire of serine/threonine kinase receptors , 1992, Cell.

[10]  R. Weinberg,et al.  Expression cloning and characterization of the TGF-β type III receptor , 1991, Cell.

[11]  L. Mathews,et al.  Expression cloning of an activin receptor, a predicted transmembrane serine kinase , 1991, Cell.

[12]  J. Massagué,et al.  Distinct transforming growth factor-beta (TGF-beta) receptor subsets as determinants of cellular responsiveness to three TGF-beta isoforms. , 1990, The Journal of biological chemistry.

[13]  J. Massagué,et al.  Concomitant loss of transforming growth factor (TGF)-beta receptor types I and II in TGF-beta-resistant cell mutants implicates both receptor types in signal transduction. , 1990, The Journal of biological chemistry.

[14]  D. Riddle,et al.  daf-1, a C. elegans gene controlling dauer larva development, encodes a novel receptor protein kinase , 1990, Cell.

[15]  Michael Loran Dustin,et al.  The arrangement of the immunoglobulin-like domains of ICAM-1 and the binding sites for LFA-1 and rhinovirus , 1990, Cell.

[16]  R. Derynck,et al.  Human Transforming Growth Factor- β3: Recombinant Expression, Purification, and Biological Activities in Comparison with Transforming Growth Factors-β 1 and -β2 , 1989 .

[17]  N. Proudfoot.  How RNA polymerase II terminates transcription in higher eukaryotes. , 1989, Trends in biochemical sciences.

[18]  P. Segarini,et al.  Binding of transforming growth factor-beta to cell surface proteins varies with cell type. , 1989, Molecular endocrinology.

[19]  Kathryn S. Prickett,et al.  A Short Polypeptide Marker Sequence Useful for Recombinant Protein Identification and Purification , 1988, Bio/Technology.

[20]  M J Banda,et al.  Wound macrophages express TGF-alpha and other growth factors in vivo: analysis by mRNA phenotyping. , 1988, Science.

[21]  T. Hunter,et al.  The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. , 1988, Science.

[22]  I. Herskowitz.  Functional inactivation of genes by dominant negative mutations , 1987, Nature.

[23]  G. Heijne.  A new method for predicting signal sequence cleavage sites. , 1986 .

[24]  B. Howard,et al.  High efficiency DNA-mediated transformation of primate cells. , 1983, Science.

[25]  J. Massagué,et al.  Transforming growth factor-beta inhibition of epithelial cell proliferation linked to the expression of a 53-kDa membrane receptor. , 1989, The Journal of biological chemistry.

[26]  A. Smith,et al.  DNA sequence analysis by primed synthesis. , 1980, Methods in enzymology.