The gene structure of the human growth factor bound protein GRB2

被引:2
作者
Bochmann, H [1 ]
Gehrisch, S [1 ]
Jaross, W [1 ]
机构
[1] Tech Univ Dresden Klinikum, Inst Klin Chem & Lab Med, D-01307 Dresden, Germany
关键词
D O I
10.1006/geno.1998.5692
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
The growth factor bound protein GrRB2, a 25-kDa cytosolic protein, plays a key role in two separate pathways of the insulin signal transduction system leading from the insulin receptor to the Ras proteins and thus affecting mitogenic signaling. GRB2 regulates Ras activation through association with the guanine nucleotide exchange factor Sos. The GRB2/Sos complex can connect with insulin receptor substrate 1 (IRS-1), which is one of the primary targets of the insulin and insulin-like growth factor receptors. In a second pathway, independent of IRS-1, GRB2 links the insulin receptor to Ras signaling through another adapter protein, called Shc. In protooncogenic and other noninsulin signaling systems, GRB2 appears to link receptor tyrosine kinases to Ras in similar pathways as well. This study presents the exon-intron organization of the human GRB2 gene. After primers were placed across the known mRNA sequence, Long PCR products spanning introns and their adjacent splice sites were amplified and adequately sequenced to establish the splice sites and flanking regions. The gene was found to consist of five exons (ranging from 78 to 186 bp) and of four introns (from similar to 1 to similar to 7 kb). Intron primers for the respective exons were generated using the newly found flanking sequences. All exons were successfully amplified and sequenced, and the data obtained from Long PCR sequencing were confirmed. (C) 1999 Academic Press.
引用
收藏
页码:203 / 207
页数:5
相关论文
共 24 条
[1]   HUMAN SKELETAL-MUSCLE INSULIN-RECEPTOR SUBSTRATE-1 - CHARACTERIZATION OF THE CDNA, GENE, AND CHROMOSOMAL LOCALIZATION [J].
ARAKI, E ;
SUN, XJ ;
HAAG, BL ;
CHUANG, LM ;
ZHANG, Y ;
YANGFENG, TL ;
WHITE, MF ;
KAHN, CR .
DIABETES, 1993, 42 (07) :1041-1054
[2]   PHOSPHATIDYLINOSITOL 3'-KINASE IS ACTIVATED BY ASSOCIATION WITH IRS-1 DURING INSULIN STIMULATION [J].
BACKER, JM ;
MYERS, MG ;
SHOELSON, SE ;
CHIN, DJ ;
SUN, XJ ;
MIRALPEIX, M ;
HU, P ;
MARGOLIS, B ;
SKOLNIK, EY ;
SCHLESSINGER, J ;
WHITE, MF .
EMBO JOURNAL, 1992, 11 (09) :3469-3479
[3]   PCR AMPLIFICATION OF UP TO 35-KB DNA WITH HIGH-FIDELITY AND HIGH-YIELD FROM LAMBDA-BACTERIOPHAGE TEMPLATES [J].
BARNES, WM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (06) :2216-2220
[4]   Interleukin 5 signals through Shc and Grb2 in human eosinophils [J].
Bates, ME ;
Busse, WW ;
Bertics, PJ .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 1998, 18 (01) :75-83
[5]   EPIDERMAL GROWTH-FACTOR REGULATES P21(RAS) THROUGH THE FORMATION OF A COMPLEX OF RECEPTOR, GRB2 ADAPTER PROTEIN, AND SOS NUCLEOTIDE EXCHANGE FACTOR [J].
BUDAY, L ;
DOWNWARD, J .
CELL, 1993, 73 (03) :611-620
[6]   Prediction of complete gene structures in human genomic DNA [J].
Burge, C ;
Karlin, S .
JOURNAL OF MOLECULAR BIOLOGY, 1997, 268 (01) :78-94
[7]  
DALY RJ, 1994, ONCOGENE, V9, P2723
[8]   THE GRB2/SEM-5 ADAPTER PROTEIN [J].
DOWNWARD, J .
FEBS LETTERS, 1994, 338 (02) :113-117
[9]   A tyrosine-phosphorylated protein of 140 kD is constitutively associated with the phosphotyrosine binding domain of Shc and the SH3 domains of Grb2 in acute myeloid leukemia cells [J].
Jucker, M ;
Schiffer, CA ;
Feldman, RA .
BLOOD, 1997, 89 (06) :2024-2035
[10]   THE SCANNING MODEL FOR TRANSLATION - AN UPDATE [J].
KOZAK, M .
JOURNAL OF CELL BIOLOGY, 1989, 108 (02) :229-241