Regulation of cell proliferation by epidermal growth factor

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.     

Topology independent protein structural alignment

Background  

Identifying structurally similar proteins with different chain topologies can aid studies in homology modeling, protein folding, protein design, and protein evolution. These include circular permuted protein structures, and the more general cases of non-cyclic permutations between similar structures, which are related by non-topological rearrangement beyond circular permutation. We present a method based on an approximation algorithm that finds sequence-order independent structural alignments that are close to optimal. We formulate the structural alignment problem as a special case of the maximum-weight independent set problem, and solve this computationally intensive problem approximately by iteratively solving relaxations of a corresponding integer programming problem. The resulting structural alignment is sequence order independent. Our method is also insensitive to insertions, deletions, and gaps.     

我国巴拉巴按蚊形态描述

白踝按蚊种团是由很多形态近似的蚊种组成,其中巴拉巴按蚊和白踝按蚊均为东南亚一带的重要传疟媒介。我国过去资料均记载为白踝按蚊,但未从形态上详细鉴定。为了确定该种的分类地位,1963年作者等在海南岛万宁县兴隆附近山林区采集“白踝按蚊”全套标本10批共150多套,1971年后从云南省采集少数标本进行形态鉴定,发现其与Colless(1956,1957)所描述的白踝按蚊Anopheles leucosphyrus leucosphyrus Donitz(1901)有很明显的差别,而与巴拉巴按蚊A.balabacensis balabacensis Balsas(1936)除某些特征略有差异外,余均完全一致。按Colless的分类法,过去我国记载的“白踝按蚊”,应鉴定为巴拉巴按蚊A.balabacensis balabacensis Baisas。     

Ghrelin在小鼠体内早期胚胎发育中的表达

为了探讨Ghrelin是否在昆明系小白鼠(Mus musculus)体内早期胚胎发育中发挥作用。运用激素超排卵技术及动物解剖学方法获取小鼠体内不同发育阶段的早期胚胎,应用实时定量PCR技术检测了Ghrelin mRNA的相对表达量。结果表明,Ghrelin mRNA在小鼠各期胚胎中均有表达;同时,GhrelinmRNA的表达量呈现一定规律性变化,2-细胞期表达量最低,8-细胞期表达量达到最高值,总体趋势是先降低后升高之后又降低。研究结果揭示,Ghrelin可能在小鼠早期胚胎发育中发挥一定的作用。