We recently reported the isolation of a chicken cDNA clone encoding a basic fibroblast growth factor (FGF) receptor that has three immunoglobulinlike domains in the extraceliular region. We embryogenesis (19, 45).FGFs also exhibit potent angiogenic activities (12). It is thought that the angiogenic activity of FGFs is due in large part to the chemotactic and mitogenic effects of these factors on endothelial cells. In addition, constitutive expression of FGFs has been shown to induce cellular transformation in transfected cells (17,34,38), indicating that autocrine or paracrine stimulation by FGFs may be involved in tumor formation.Recently, additional members of the FGF family of proteins have been identified on the basis of amino acid sequence homologies. These proteins exhibit approximately 35 to 45% amino acid identity with aFGF and bFGF and include the product of the int-2 oncogene (29), the product of the hst oncogene (Kaposi sarcoma FGF) (6, 46), FGF-5 (55), FGF-6 (26), and keratinocyte growth factor (39 Vol.

The cellular transcription factor E2F appears to be a target for the regulatory action of the retinoblastoma tumor suppressor gene product. The recent isolation of the E2F1 cDNA clone, which encodes a polypeptide with properties characteristic of E2F, has now allowed a more detailed analysis of the regulation of E2F function by Rb as well as the Rb-related p107 protein and the adenovirus 19-kDa E4 gene product. Previous experiments have shown that each of these regulatory proteins can modulate the activity of cellular E2F. We find that each of these regulatory events can be mediated through the E2F1 product. Moreover, an examination of various E2F1 mutations reveals distinct specificities for these regulatory proteins. For instance, the ability of E4 to alter E2F1 function is dependent upon sequences within a putative leucine repeat of E2F1 as well as within the C-terminal acidic domain. In contrast, the leucine repeat element was not important for Rb-or p107-mediated inhibition of E2F1 activity. Although the C-terminal acidic domain of E2F1, previously shown to be important for Rb binding, appears to be a site for regulation of E2F1 by Rb and p107, point mutations within this region distinguish recognition by Rb and p107. These results underscore the complexity of E2F regulatory interactions and also demonstrate a qualitative distinction in the interactions of Rb and p107 with E2F1, perhaps reflective of functional differences.The E2F transcription factor was originally identified as a cellular DNA-binding protein that recognized and bound to two adjacent elements in the adenovirus E2 promoter, sites that were critical for ElA-mediated activation of E2 transcription (31). Subsequent studies demonstrated that a product of the adenovirus E4 gene, a 19-kDa polypeptide, interacted with E2F and in so doing facilitated cooperative binding to the adjacent E2F sites (21,22,27,41,48). More recent work has shown that in most cell types, E2F is normally complexed to other cellular proteins and that these complexes cannot bind the E4 protein (1). The adenovirus ElA protein is capable of disrupting these complexes, thus allowing E4 to interact with E2F and form a stable complex on the E2 promoter (1).The identification of the components of these E2F complexes has shed considerable light on the normal cellular role of E2F and the role of ElA, as well as other DNA tumor virus oncoproteins, in stimulating transcription and promoting oncogenesis (for a review, see reference 43). All of the proteins found in association with E2F were previously identified as proteins interacting with ElA, T antigen, and E7. These include the retinoblastoma gene product [2,4,8,9], the Rb-related p107 protein (6,14,44,54), and the cell cycle regulatory proteins cyclin A and cdk2 (3,6,14,40,44). It appears that as a consequence of the interaction of ElA with these proteins, the E2F complexes are disrupted and E2F is released.A variety of experiments have now shown that the interaction of Rb with E2F inhibits the transcriptional activating capaci...

Oxidative stress is a potential component of the final common pathway leading to apoptosis following many diverse stimuli. Here, we document that the oxidant paraquat caused apoptosis in mouse 32D cells. We examined early paraquat-induced lipid peroxidation after metabolic incorporation of the oxidant-sensitive fluorescent fatty acid cis-parinaric acid (cis-PA) into phospholipids and high-performance liquid chromatography separation of specific phospholipid classes. Paraquat induced peroxidation of cis-PA primarily in phosphatidylserine (PS) and to a lesser extent in phosphatidylinositol (PI) within 2 h. The selective oxidation of PS occurred before signs of cytotoxicity and preceded the externalization of PS as assessed by annexin V binding. Overexpression of Bcl-2 afforded significant protection against paraquat-induced apoptosis, early PS and PI oxidation, and PS externalization but not the ultimate formation of high-molecular-weight DNA fragments. Therefore, both selective phospholipid peroxidation and DNA damage occurred after paraquat exposure, but only the former was specifically associated with apoptosis. We suggest Bcl-2 may inhibit oxidant-induced apoptosis by preventing the peroxidation of specific membrane phospholipids.

Plasmodium falciparum is an intracellular parasite of the red blood cell. During development it exports proteins which are transported to specific locations within the host erythrocyte. We have begun to identify and characterize exported membrane proteins of P. falciparum in order to obtain specific marker molecules for the study of the mechanisms involved in the distribution of parasite-derived proteins within the host cell. In this report we describe the characterization of a 35 kDa protein which is recognized by a monoclonal antibody. The protein is tightly associated with membranes isolated from infected erythrocytes; it is resistant to extraction with alkali and soluble after treatment with detergents. It is located at the membrane of the parasitophorous vacuole and in membrane-bound compartments which appear in the cytoplasm of the infected erythrocyte. The protein co-localizes with the previously described exported protein-1 (exp-1). Considering its localization and physical similarities to exp-1, we name the 35 kDa protein the exported protein-2 (exp-2).