Transforming growth factor-beta 2: cDNA cloning and sequence analysis.

We have obtained a cDNA clone coding for human transforming growth factor (TGF)-beta 2. The clone was isolated from a tamoxifen-treated human prostatic adenocarcinoma cell line (PC-3) using oligonucleotide probes based on the partial amino acid sequence of purified TGF-beta 2. The cDNA sequence predicts that TGF-beta 2 is synthesized as a 442-amino-acid polypeptide precursor from which the mature 112-amino-acid TGF-beta 2 subunit is derived by proteolytic cleavage. The proteins coded for by the human TGF-beta 1 and TGF-beta 2 cDNAs show an overall homology of 41%. The mature and amino-terminal precursor regions show 71% and 31% homology, respectively. Northern blot analysis identified TGF-beta 2 transcripts of 4.1, 5.1, and 6.5 kb using mRNA from several different sources. Analysis of polyadenylated RNA from tamoxifen-treated PC-3 cells showed that these cells contain higher numbers of transcripts for TGF-beta 1 than for TGF-beta 2, although they produce more TGF-beta 2 protein than TGF-beta 1. This suggests that there is a post-transcriptional level of regulation for the production of these proteins.

[1]  G. Plowman,et al.  Cloning and Sequence Analysis of Simian Transforming Growth Factor-β cDNA , 1987 .

[2]  H. Marquardt,et al.  Human transforming growth factor type beta 2: production by a prostatic adenocarcinoma cell line, purification, and initial characterization. , 1987, Biochemistry.

[3]  E. Reinherz,et al.  Molecular cloning and expression of T11 cDNAs reveal a receptor-like structure on human T lymphocytes. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[4]  J. Graycar,et al.  Cartilage-inducing factor-B is a unique protein structurally and functionally related to transforming growth factor-beta. , 1987, The Journal of biological chemistry.

[5]  J. Massagué,et al.  The transforming growth factor-β system, a complex pattern of cross-reactive ligands and receptors , 1987, Cell.

[6]  T. Rose,et al.  Bovine and human cDNA sequences encoding a putative benzodiazepine receptor ligand. , 1987, DNA.

[7]  D. Helfman,et al.  Nonmuscle and muscle tropomyosin isoforms are expressed from a single gene by alternative RNA splicing and polyadenylation , 1986, Molecular and cellular biology.

[8]  M. Sporn,et al.  Transforming growth factor-beta: biological function and chemical structure. , 1986, Science.

[9]  P. Donahoe,et al.  Isolation of the bovine and human genes for müllerian inhibiting substance and expression of the human gene in animal cells , 1986, Cell.

[10]  J. McPherson,et al.  Cartilage-inducing factor-A. Apparent identity to transforming growth factor-beta. , 1986, The Journal of biological chemistry.

[11]  E. Chen,et al.  The murine transforming growth factor-beta precursor. , 1986, The Journal of biological chemistry.

[12]  M. Kozak.  Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes , 1986, Cell.

[13]  N. Ling,et al.  Complementary DNA sequences of ovarian follicular fluid inhibin show precursor structure and homology with transforming growth factor-β , 1985, Nature.

[14]  Anita B. Roberts,et al.  Human transforming growth factor-β complementary DNA sequence and expression in normal and transformed cells , 1985, Nature.

[15]  D. Rosen,et al.  Purification and characterization of two cartilage-inducing factors from bovine demineralized bone. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[16]  H. Moses,et al.  Growth inhibitor from BSC-1 cells closely related to platelet type beta transforming growth factor. , 1984, Science.

[17]  S. Henikoff.  Unidirectional digestion with exonuclease III creates targeted breakpoints for DNA sequencing. , 1984, Gene.

[18]  M. Sporn,et al.  Transforming growth factor-beta in human platelets. Identification of a major storage site, purification, and characterization. , 1983, The Journal of biological chemistry.

[19]  Gunnar von Heijne,et al.  Patterns of Amino Acids near Signal‐Sequence Cleavage Sites , 1983 .

[20]  H. Moses,et al.  Comparison of intra- and extracellular transforming growth factors from nontransformed and chemically transformed mouse embryo cells. , 1983, Cancer research.

[21]  R. Cortese,et al.  pEMBL: a new family of single stranded plasmids. , 1983, Nucleic acids research.

[22]  C. B. Childs,et al.  Serum contains a platelet-derived transforming growth factor. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[23]  G. Fareed,et al.  Transformation of human embryonic kidney cells by human papovarirus BK , 1979, Journal of virology.

[24]  H. Boedtker,et al.  RNA molecular weight determinations by gel electrophoresis under denaturing conditions, a critical reexamination. , 1977, Biochemistry.

[25]  N. Proudfoot,et al.  3′ Non-coding region sequences in eukaryotic messenger RNA , 1976, Nature.

[26]  M. Sporn,et al.  Purification and initial characterization of a type f8 transforming growth factor from human placenta , 2003 .

[27]  W. Gelbart,et al.  A transcript from a Drosophila pattern gene predicts a protein homologous to the transforming growth factor-β family , 1987, Nature.

[28]  D. Twardzik,et al.  Transforming growth factor (TGF) activity in human urine: Synergism between TFG‐beta and urogastrone , 1985, Journal of cellular biochemistry.