Schlessinger J, Schreiber A B, Levi A, Lax I, Libermann T, Yarden Y
CRC Crit Rev Biochem. 1983;14(2):93-111. doi: 10.3109/10409238309102791.
Epidermal Growth Factor (EGF) is a 6045 dalton polypeptide which stimulates the proliferation of various cell types in vitro and in vivo. EGF binds to diffusely distributed membrane receptors which rapidly cluster primarily on coated pits areas on the plasma membrane. Subsequently, the EGF-receptor complexes are endocytosed and degraded by lysosomal enzymes. The lateral diffusion coefficient (D) of EGF-receptor complexes on cultured cells increases gradually from D = 2.8 X 10(-10) cm2/sec at 5 degrees C to 8.5 X 10(-10) cm2/sec at 37 degrees C. In the same range of temperature the rotational correlation times change from 25 to 50 microseconds to approximately 350 microseconds. Hence, at 4 degrees C, the occupied EGF receptors translate and rotate rapidly in the plane of the membrane. At 37 degrees C, EGF receptors form microclusters composed of 10 to 50 molecules. Moreover, it is concluded that both at 4 degrees C and 37 degrees C lateral diffusion of the occupied receptors is not the rate determining step for either receptor clustering or internalization. EGF receptor is a 150,000 to 170,000 dalton glycoprotein. The receptor is in close proximity to an EGF-sensitive, cAMP-independent, tyrosine-specific protein kinase which also phosphorylates the receptor molecules itself. The EGF sensitive kinase is similar to the kinase activity which is associated with certain RNA tumor viruses. The fact that the non-mitogenic cyanogen-bromide cleaved EGF is as potent as native EGF in stimulating phosphorylation suggests that EGF-induced, protein phosphorylation is a necessary but insufficient signal for the induction of DNA synthesis by EGF. EGF receptor serves also as the binding site for Transforming Growth Factors (TGF) which compete with EGF and induce anchorage-independent growth of normal cells in soft agar. Tumor promoters such as phorbol ester effect the binding of EGF to its membrane receptors and its ability to stimulate DNA synthesis. EGF itself has also some tumor promoting activity. Hence, the membrane receptor for EGF seems to participate in the regulation of normal and neoplastic growth. Monoclonal antibodies against EGF receptor (IgM) induce various early and delayed effects of EGF, while their monovalent Fab' fragments are devoid of biological activity. These observations support the notions that EGF receptor rather than EGF itself is the active moiety and that the role of the hormone is to perturb the receptor in the appropriate way, probably by inducing the microaggregation of EGF receptors.
表皮生长因子（EGF）是一种6045道尔顿的多肽，它在体内外均可刺激多种细胞类型的增殖。EGF与广泛分布的膜受体结合，这些受体迅速聚集，主要集中在质膜上的被膜小窝区域。随后，EGF-受体复合物被内吞，并被溶酶体酶降解。培养细胞上EGF-受体复合物的侧向扩散系数（D）从5℃时的D = 2.8×10⁻¹⁰ cm²/秒逐渐增加到37℃时的8.5×10⁻¹⁰ cm²/秒。在相同温度范围内，旋转相关时间从25至50微秒变化到约350微秒。因此，在4℃时，被占据的EGF受体在膜平面内快速平移和旋转。在37℃时，EGF受体形成由10至50个分子组成的微簇。此外，可以得出结论，在4℃和37℃时，被占据受体的侧向扩散对于受体聚集或内化均不是速率决定步骤。EGF受体是一种150,000至170,000道尔顿的糖蛋白。该受体紧邻一种对EGF敏感、不依赖cAMP的酪氨酸特异性蛋白激酶，该激酶也可使受体分子自身磷酸化。EGF敏感激酶类似于与某些RNA肿瘤病毒相关的激酶活性。非促有丝分裂的溴化氰裂解的EGF在刺激磷酸化方面与天然EGF一样有效，这一事实表明，EGF诱导的蛋白质磷酸化是EGF诱导DNA合成的必要但不充分的信号。EGF受体也是转化生长因子（TGF）的结合位点，TGF与EGF竞争，并诱导正常细胞在软琼脂中进行不依赖贴壁的生长。肿瘤促进剂如佛波酯会影响EGF与其膜受体的结合及其刺激DNA合成的能力。EGF本身也具有一定的肿瘤促进活性。因此，EGF的膜受体似乎参与正常和肿瘤生长的调节。针对EGF受体的单克隆抗体（IgM）可诱导EGF的各种早期和延迟效应，而其单价Fab'片段则无生物学活性。这些观察结果支持以下观点：EGF受体而非EGF本身是活性部分，并且激素的作用可能是通过诱导EGF受体的微聚集以适当方式干扰受体。
