ANTIGENIC STRUCTURE OF BOVINE GROWTH-HORMONE - LOCATION OF A GROWTH ENHANCING REGION

被引:28
作者
ASTON, R
RATHJEN, DA
HOLDER, AT
BENDER, V
TRIGG, TE
COWAN, K
EDWARDS, JA
COWDEN, WB
机构
[1] PEPTIDE TECHNOL LTD,DEE WHY,NSW 2099,AUSTRALIA
[2] INST GRASSLANDS & ANIM PROD,MAIDENHEAD SL6 5LR,BERKS,ENGLAND
[3] AUSTRALIAN NATL UNIV,JOHN CURTIN SCH MED RES,DEPT EXPTL PATHOL,CANBERRA,ACT 2601,AUSTRALIA
关键词
D O I
10.1016/0161-5890(91)90085-X
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Site-directed antisera generated by peptide immunization have been used to study the antigenicity of bovine growth hormone (bGH). Prediction of sequential antigenic sites has been performed using secondary structure information derived from the 'Protean' prediction routine. The structures predicted by this programme agree closely with the corresponding structure of GH recently derived from crystallographic studies. We have previously shown that the binding of monoclonal antibodies of particular epitope specificity to human or bovine GH results in significant enhancement of hormonal activity in vivo; however, the sites recognized by these antibodies were not known. Here we identify a sequence region, corresponding to a loop structure joining helices 3 and 4, which, is associated with the growth enhancement phenomenon. Antisera raised to either of two overlapping peptides (residues 120-140 and 134-154) significantly increase the biological activity of GH in vivo. Antisera directed to other regions on the GH molecule failed to demonstrate this property. Coincidentally, the sites recognized by the growth-enhancing anti-peptide antisera overlap with the site on GH which is highly susceptible to proteolytic cleavage; such cleavage has been shown in some cases to result in hormone enhancement.
引用
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页码:41 / 50
页数:10
相关论文
共 49 条
[1]   3-DIMENSIONAL STRUCTURE OF A GENETICALLY ENGINEERED VARIANT OF PORCINE GROWTH-HORMONE [J].
ABDELMEGUID, SS ;
SHIEH, HS ;
SMITH, WW ;
DAYRINGER, HE ;
VIOLAND, BN ;
BENTLE, LA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (18) :6434-6437
[2]   MONOCLONAL-ANTIBODIES TO HUMAN GROWTH-HORMONE CAN DISTINGUISH BETWEEN PITUITARY AND GENETICALLY ENGINEERED FORMS [J].
ASTON, R ;
COOPER, L ;
HOLDER, A ;
IVANYI, J ;
PREECE, M .
MOLECULAR IMMUNOLOGY, 1985, 22 (03) :271-275
[3]   POTENTIATION OF THE SOMATOGENIC AND LACTOGENIC ACTIVITY OF HUMAN GROWTH-HORMONE WITH MONOCLONAL-ANTIBODIES [J].
ASTON, R ;
HOLDER, AT ;
PREECE, MA ;
IVANYI, J .
JOURNAL OF ENDOCRINOLOGY, 1986, 110 (03) :381-388
[4]   ANTIGENIC, RECEPTOR-BINDING AND MITOGENIC ACTIVITY OF PROTEOLYTIC FRAGMENTS OF HUMAN GROWTH-HORMONE [J].
ASTON, R ;
IVANYI, J .
EMBO JOURNAL, 1983, 2 (04) :493-497
[5]   MONOCLONAL-ANTIBODIES TO GROWTH-HORMONE AND PROLACTIN [J].
ASTON, R ;
IVANYI, J .
PHARMACOLOGY & THERAPEUTICS, 1985, 27 (03) :403-424
[6]   ENHANCEMENT OF BOVINE GROWTH-HORMONE ACTIVITY INVIVO BY MONOCLONAL-ANTIBODIES [J].
ASTON, R ;
HOLDER, AT ;
IVANYI, J ;
BOMFORD, R .
MOLECULAR IMMUNOLOGY, 1987, 24 (02) :143-150
[7]   SOLID-PHASE PEPTIDE-SYNTHESIS USING N-ALPHA-FLUORENYLMETHOXYCARBONYLAMINO ACID PENTAFLUOROPHENYL ESTERS [J].
ATHERTON, E ;
SHEPPARD, RC .
JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS, 1985, (03) :165-166
[8]   USE OF CALCIUM DEPENDENCE AS A MEANS TO STUDY THE INTERACTION BETWEEN GROWTH-HORMONES AND THEIR BINDING-PROTEINS IN RABBIT LIVER [J].
BARNARD, R ;
WATERS, MJ .
BIOCHEMICAL JOURNAL, 1988, 250 (02) :533-538
[9]   EVIDENCE FROM THE USE OF MONOCLONAL-ANTIBODY PROBES FOR STRUCTURAL HETEROGENEITY OF THE GROWTH-HORMONE RECEPTOR [J].
BARNARD, R ;
BUNDESEN, PG ;
RYLATT, DB ;
WATERS, MJ .
BIOCHEMICAL JOURNAL, 1985, 231 (02) :459-468
[10]   PROTECTION AGAINST FOOT-AND-MOUTH-DISEASE BY IMMUNIZATION WITH A CHEMICALLY SYNTHESIZED PEPTIDE PREDICTED FROM THE VIRAL NUCLEOTIDE-SEQUENCE [J].
BITTLE, JL ;
HOUGHTEN, RA ;
ALEXANDER, H ;
SHINNICK, TM ;
SUTCLIFFE, JG ;
LERNER, RA ;
ROWLANDS, DJ ;
BROWN, F .
NATURE, 1982, 298 (5869) :30-33