RECOVERY OF MITOGENIC ACTIVITY OF A GROWTH-FACTOR MUTANT WITH A NUCLEAR TRANSLOCATION SEQUENCE

被引:365
作者
IMAMURA, T [1 ]
ENGLEKA, K [1 ]
ZHAN, X [1 ]
TOKITA, Y [1 ]
FOROUGH, R [1 ]
ROEDER, D [1 ]
JACKSON, A [1 ]
MAIER, JAM [1 ]
HLA, T [1 ]
MACIAG, T [1 ]
机构
[1] AMER RED CROSS,JEROME H HOLLAND LAB BIOMED SCI,MOLEC BIOL LAB,15601 CRABBS BRANCH WAY,ROCKVILLE,MD 20855
关键词
D O I
10.1126/science.1699274
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Heparin-binding growth factor-1 (HBGF-1) is an angiogenic polypeptide mitogen for mesoderm- and neuroectoderm-derived cells in vitro and remains biologically active after truncation of the amino-terminal domain (HBGF-1α) of the HBGF-1β precursor. Polymerase chain reaction mutagenesis and prokaryotic expression systems were used to prepare a mutant of HBGF-1α lacking a putative nuclear translocation sequence (amino acid residues 21 to 27; HBGF-1U). Although HBGF-1U retains its ability to bind to heparin, HBGF-1U fails to induce DNA synthesis and cell proliferation at concentrations sufficient to induce intracellular receptor-mediated tyrosine phosphorylation and c-fos expression. Attachment of the nuclear translocation sequence from yeast histone 2B at the amino terminus of HBGF-1U yields a chimeric polypeptide (HBGF-1U2) with mitogenic activity in vitro and indicates that nuclear translocation is important for this biological response.
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页码:1567 / 1570
页数:4
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