Fuhrmann V, Kinkl N, Leveillard T, Sahel J, Hicks D
Laboratoire de Physiopathologie Cellulaire et Moleculaire de la Retine, Clinique Medicale A, INSERM-CHUR-Universite Louis Pasteur, Centre Hospitalier Regional Universitaire, Strasbourg, France.
J Mol Neurosci. 1999 Aug-Oct;13(1-2):187-97. doi: 10.1385/JMN:13:1-2:187.
The fibroblast growth factor (FGF) family, with its prototype members acidic FGF (FGF-1) and basic FGF (FGF-2), binds to four related receptor tyrosine kinases, termed FGFR1, R2, R3, and R4, expressed on most types of cells in tissue culture. In many respects, the FGFR appear similar to other growth factor receptors; thus, dimerization of receptor monomers on ligand binding is likely to be a requisite for activation of the kinase domains, leading to receptor trans-phosphorylation. Within the central nervous system (CNS), including retina, FGFR1 and R2 have been widely described as the predominant forms. FGFR4 is reported to be strongly expressed only during early stages of development, and apart from one small region (the lateral habenular nucleus) is not detectable in adult CNS. Screening of different neural and nonneural tissues by reverse transcriptase-polymerase chain reaction (RT-PCR) revealed that whereas FGFR1 and R2 were strongly expressed in adult cortex, cerebellum, retina, and kidney, robust FGFR4 expression was only seen in retina and kidney. FGFR4 mRNA was present within fractions of the outer and inner nuclear layers isolated from adult rat retinas, and could also be detected in pure photoreceptor cultures prepared from young rat retinas. On the contrary, FGFR4 mRNA could not be detected in primary cultures of retinal Müller glia or pigment epithelium, indicating specific enrichment in retinal neurons. In situ hybridization studies of adult rat retina showed FGFR4 expression in all retinal cellular layers, especially prominent in the outer nuclear layer. FGFR4 protein was detected by immunoblotting of homogenates of rat retina, with specific antibody binding to bands at 115, 47, and 30 kDa. FGFR4 mRNA and protein were also reliably detected in postmortem adult human retina. The potential roles of these signal transduction molecules in FGF-induced biological responses in the retina are discussed.
成纤维细胞生长因子（FGF）家族以其原型成员酸性FGF（FGF-1）和碱性FGF（FGF-2）为代表，可与四种相关的受体酪氨酸激酶结合，分别称为FGFR1、R2、R3和R4，这些激酶在组织培养中的大多数细胞类型上均有表达。在许多方面，FGFR与其他生长因子受体相似；因此，配体结合时受体单体的二聚化可能是激酶结构域激活的必要条件，从而导致受体的反式磷酸化。在包括视网膜在内的中枢神经系统（CNS）中，FGFR1和R2被广泛描述为主要形式。据报道，FGFR4仅在发育早期强烈表达，除了一个小区域（外侧缰核）外，在成年CNS中无法检测到。通过逆转录聚合酶链反应（RT-PCR）对不同神经和非神经组织进行筛选发现，FGFR1和R2在成年皮质、小脑、视网膜和肾脏中强烈表达，而FGFR4仅在视网膜和肾脏中大量表达。FGFR4 mRNA存在于从成年大鼠视网膜分离的外核层和内核层部分中，在从幼鼠视网膜制备的纯光感受器培养物中也可检测到。相反，在视网膜Müller胶质细胞或色素上皮的原代培养物中未检测到FGFR4 mRNA，表明其在视网膜神经元中特异性富集。成年大鼠视网膜的原位杂交研究表明，FGFR4在所有视网膜细胞层中均有表达，在外核层尤为突出。通过用特异性抗体与115、47和30 kDa的条带结合，对大鼠视网膜匀浆进行免疫印迹检测到了FGFR4蛋白。在死后的成年人类视网膜中也可靠地检测到了FGFR4 mRNA和蛋白。本文讨论了这些信号转导分子在FGF诱导的视网膜生物学反应中的潜在作用。
