Physicochemical Activation of Recombinant Latent Transforming Growth Factor-beta's 1, 2, and 3

被引:334
作者
Brownh, Peter D. [1 ]
Wakefiel, Lalage M. [1 ]
Levinson, Arthur D. [2 ]
Sporn, Michael B. [1 ]
机构
[1] NCI, Chemoprevent Lab, Bldg 41,Room C629, Bethesda, MD 20892 USA
[2] Genentech Inc, Dept Cell Genet, San Francisco, CA 94080 USA
关键词
transforming growth factor-beta; latent complexes; recombinant methods;
D O I
10.3109/08977199009037500
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Native and recombinant forms of transforming growth factor-beta 1 (TGF-beta 1) are synthesized predominantly as biologically latent complexes. Physicochemical analysis demonstrates that the more recently described TGF-beta 2 and TGF-beta 3 are also latent, and reveals a common series of sharply defined parameters for activation. Human recombinant latent TGF-beta's 1 and 2 show identical profiles of activation by acid and base; the transition from latency occurs between pH 4.1 and 3.1, and between pH 11.0 and 11.9. The profile for chicken recombinant latent TGF-beta 3 is slightly shifted with activation between pH 3.1 and 2.5, and between pH 10.0 and 12.3. Thermal activation of native and recombinant latent TGF-beta 1 occurs over the temperature ranges of 75-100 degrees C and 65-100 degrees C, respectively, with complete activation after 5 min at 8 degrees C. Temperatures above 90 degrees C result in thermal denaturation of TGF-beta 1 itself. Recombinant latent TGF-beta's 2 and 3 are also activated over this temperature range; however, maximum activation occurs at 100 degrees C. These results suggest common elements in latent complex structure despite differences between the TGF-beta subtypes in pro-region primary sequence.
引用
收藏
页码:35 / 43
页数:10
相关论文
共 23 条
[11]  
OCONNORMCCOURT MD, 1987, J BIOL CHEM, V262, P14090
[12]   ACTIVATION OF THE BONE-DERIVED LATENT TGF BETA-COMPLEX BY ISOLATED OSTEOCLASTS [J].
OREFFO, ROC ;
MUNDY, GR ;
SEYEDIN, SM ;
BONEWALD, LF .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1989, 158 (03) :817-823
[13]   BETA-TRANSFORMING GROWTH-FACTOR IS STORED IN HUMAN-BLOOD PLATELETS AS A LATENT HIGH-MOLECULAR-WEIGHT COMPLEX [J].
PIRCHER, R ;
JULLIEN, P ;
LAWRENCE, DA .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1986, 136 (01) :30-37
[14]  
Roberts A. B, 1989, PEPTIDE GROWTH FACTO
[15]   TRANSFORMING GROWTH-FACTOR TYPE-BETA - RAPID INDUCTION OF FIBROSIS AND ANGIOGENESIS INVIVO AND STIMULATION OF COLLAGEN FORMATION INVITRO [J].
ROBERTS, AB ;
SPORN, MB ;
ASSOIAN, RK ;
SMITH, JM ;
ROCHE, NS ;
WAKEFIELD, LM ;
HEINE, UI ;
LIOTTA, LA ;
FALANGA, V ;
KEHRL, JH ;
FAUCI, AS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1986, 83 (12) :4167-4171
[16]  
ROBERTS AB, 1988, RECENT PROG HORM RES, V44, P157
[17]   BIOLOGICAL PROPERTIES OF HUMAN C-HA-RAS 1 GENES MUTATED AT CODON-12 [J].
SEEBURG, PH ;
COLBY, WW ;
CAPON, DJ ;
GOEDDEL, DV ;
LEVINSON, AD .
NATURE, 1984, 312 (5989) :71-75
[18]   MICROELECTRODE STUDIES ON THE ACID MICROENVIRONMENT BENEATH ADHERENT MACROPHAGES AND OSTEOCLASTS [J].
SILVER, IA ;
MURRILLS, RJ ;
ETHERINGTON, DJ .
EXPERIMENTAL CELL RESEARCH, 1988, 175 (02) :266-276
[19]   TRANSFORMING GROWTH-FACTOR-BETA - BIOLOGICAL FUNCTION AND CHEMICAL-STRUCTURE [J].
SPORN, MB ;
ROBERTS, AB ;
WAKEFIELD, LM ;
ASSOIAN, RK .
SCIENCE, 1986, 233 (4763) :532-534
[20]   SOME RECENT ADVANCES IN THE CHEMISTRY AND BIOLOGY OF TRANSFORMING GROWTH-FACTOR-BETA [J].
SPORN, MB ;
ROBERTS, AB ;
WAKEFIELD, LM ;
DECROMBRUGGHE, B .
JOURNAL OF CELL BIOLOGY, 1987, 105 (03) :1039-1045