Jin Y, Pasumarthi K B, Bock M E, Lytras A, Kardami E, Cattini P A
Department of Physiology, University of Manitoba, Winnipeg, Canada.
J Mol Cell Cardiol. 1994 Nov;26(11):1449-59. doi: 10.1006/jmcc.1994.1164.
Basic (b) fibroblast growth factor (FGF) mediates various biological responses including mitogenesis and angiogenesis by binding to specific cell surface receptors of the tyrosine kinase family. The bFGF receptor-1 FGFR1) exists in short and long isoforms due to alternate RNA splicing. Minor alterations in the amino acid sequence have also led to reports of different FGFR1 isoforms in different tissues even in the same species. In the absence of any sequence for heart FGFR1 and accumulating evidence for a role of bFGF in heart growth and differentiation, we cloned FGFR1 from embryonic mouse hearts. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to generate full-length short (2259 base pairs) and long (2526 base pairs) forms of FGFR1 cDNAs which generated 86 and 102 kDa proteins, respectively, following in vitro translation. Embryonic mouse heart FGFR1 differed by seven amino acids from the reported sequence for mouse neuroepithelial FGFR1 and appeared more similar to human placental FGFR1. A single FGFR1 transcript of approximately 4.3 kb was seen in RNA isolated from embryonic as well as adult mouse hearts. There was a decrease (approximately 8.5-fold) in FGFR1 RNA levels in the adult. The majority of FGFR1 transcripts in the adult as well as embryonic heart contained exon IIIc (FGFR1-IIIc) which is associated with isoforms that display the highest affinity for bFGF. However, the relative ratio of short versus long FGFR1 RNA expression was 0.5 in the embryonic heart compared to 5.9 in the adult heart. These results indicate that: (i) structurally distinct short and long FGFR1 isoform RNAs are expressed in the embryonic and adult heart; (ii) FGFR1-IIIc is the major form of receptor expressed in the embryonic as well as adult heart; (iii) the transition from the embryo to the adult stage is associated with a decrease but not absence of FGFR1 RNA expression; and (iv) long FGFR1-isoforms are more abundant in the embryo while short FGFR1 isoforms predominate in the adult.
碱性（b）成纤维细胞生长因子（FGF）通过与酪氨酸激酶家族的特定细胞表面受体结合，介导包括有丝分裂和血管生成在内的多种生物学反应。由于RNA可变剪接，bFGF受体1（FGFR1）存在短和长两种异构体。氨基酸序列的微小变化也导致了不同组织中甚至同一物种中不同FGFR1异构体的报道。鉴于缺乏心脏FGFR1的任何序列，且越来越多的证据表明bFGF在心脏生长和分化中起作用，我们从胚胎小鼠心脏中克隆了FGFR1。逆转录聚合酶链反应（RT-PCR）用于生成全长短（2259个碱基对）和长（2526个碱基对）形式的FGFR1 cDNA，体外翻译后分别产生86 kDa和102 kDa的蛋白质。胚胎小鼠心脏FGFR1与报道的小鼠神经上皮FGFR1序列有7个氨基酸不同，且似乎与人类胎盘FGFR1更相似。在从胚胎和成年小鼠心脏分离的RNA中均可见到一条约4.3 kb的单一FGFR1转录本。成年小鼠心脏中FGFR1 RNA水平下降（约8.5倍）。成年和胚胎心脏中的大多数FGFR1转录本都包含外显子IIIc（FGFR1-IIIc），其与对bFGF显示出最高亲和力的异构体相关。然而，胚胎心脏中短与长FGFR1 RNA表达的相对比例为0.5，而成人心脏中为5.9。这些结果表明：（i）结构不同的短和长FGFR1异构体RNA在胚胎和成年心脏中表达；（ii）FGFR1-IIIc是胚胎和成年心脏中表达的主要受体形式；（iii）从胚胎到成年阶段的转变与FGFR1 RNA表达的减少而非缺失相关；（iv）长FGFR1异构体在胚胎中更为丰富，而短FGFR1异构体在成年中占主导地位。
