Goodman S Jay, Branda Catherine S, Robinson Matthew K, Burdine Rebecca D, Stern Michael J
Department of Cell Biology, Yale University School of Medicine, I-354 SHM PO Box 208005, New Haven, CT 06520-8005, USA.
Development. 2003 Aug;130(16):3757-66. doi: 10.1242/dev.00604.
Fibroblast growth factor (FGF) receptors trigger a wide variety of cellular responses as diverse as cell migration, cell proliferation and cell differentiation. However, the molecular basis of the specificity of these responses is not well understood. The C. elegans FGF receptor EGL-15 similarly mediates a number of different responses, including transducing a chemoattractive signal and mediating an essential function. Analysis of the migration-specific alleles of egl-15 has identified a novel EGL-15 isoform that provides a molecular explanation for the different phenotypic effects of lesions at this locus. Alternative splicing yields two EGL-15 proteins containing different forms of a domain located within the extracellular region of the receptors immediately after the first IG domain. Neither of these two domain forms is found in any other FGF receptor. We have tested the roles of these EGL-15 receptor isoforms and their two FGF ligands for their signaling specificity. Our analyses demonstrate different physiological functions for the two receptor variants. EGL-15(5A) is required for the response to the FGF chemoattractant that guides the migrating sex myoblasts to their final positions. By contrast, EGL-15(5B) is both necessary and sufficient to elicit the essential function mediated by this receptor.
成纤维细胞生长因子（FGF）受体可引发多种细胞反应，如细胞迁移、细胞增殖和细胞分化等。然而，这些反应特异性的分子基础尚未完全明确。秀丽隐杆线虫的FGF受体EGL-15同样介导多种不同反应，包括转导趋化信号和介导一项重要功能。对egl-15迁移特异性等位基因的分析鉴定出一种新型EGL-15同工型，为该位点损伤的不同表型效应提供了分子解释。可变剪接产生两种EGL-15蛋白，它们在受体胞外区域紧接第一个免疫球蛋白（IG）结构域之后含有不同形式的一个结构域。这两种结构域形式在其他任何FGF受体中均未发现。我们已经测试了这些EGL-15受体同工型及其两种FGF配体的信号特异性作用。我们的分析证明这两种受体变体具有不同的生理功能。EGL-15(5A)对于对FGF趋化剂的反应是必需的，该趋化剂引导迁移的性成肌细胞到达其最终位置。相比之下，EGL-15(5B)对于引发该受体介导的重要功能既是必需的也是充分的。
