Jaana Korhonen

FGFR-4, a novel acidic fibroblast growth factor receptor with a distinct expression pattern.

We have previously identified two novel members of the fibroblast growth factor receptor (FGFR) gene family expressed in K562 erythroleukemia cells. Here we report cDNA cloning and analysis of one of these genes, named FGFR‐4. The deduced amino acid sequence of FGFR‐4 is 55% identical with both previously characterized FGFRs, flg and bek, and has the structural characteristics of a FGFR family member including three immunoglobulin‐like domains in its extracellular part. Antibodies raised against the carboxy terminus of FGFR‐4 detected 95 and 110 kd glycoproteins with a protein backbone of 88 kd in COS cells transfected with a FGFR‐4 cDNA expression vector. The FGFR‐4 protein expressed in COS cells could also be affinity‐labeled with radioiodinated acidic FGF. Furthermore, ligand binding experiments demonstrated that FGFR‐4 binds acidic FGF with high affinity but does not bind basic FGF. FGFR‐4 is expressed as a 3.0 kb mRNA in the adrenal, lung, kidney, liver, pancreas, intestine, striated muscle and spleen tissues of human fetuses. The expression pattern of FGFR‐4 is distinct from that of flg and bek and the yet additional member of the same gene family, FGFR‐3, which we have also cloned from the K562 leukemia cells. Our results suggest that FGFR‐4 along with other fibroblast growth factor receptors performs cell lineage and tissue‐specific functions.

A novel endothelial cell surface receptor tyrosine kinase with extracellular epidermal growth factor homology domains.

Endothelial cell surfaces play key roles in several important physiological and pathological processes such as blood clotting, angiogenic responses, and inflammation. Here we describe the cloning and characterization of tie, a novel type of human endothelial cell surface receptor tyrosine kinase. The extracellular domain of the predicted tie protein product has an exceptional multidomain structure consisting of a cluster of three epidermal growth factor homology motifs embedded between two immunoglobulinlike loops, which are followed by three fibronectin type III repeats next to the transmembrane region. Additionally, a cDNA form lacking the first of the three epidermal growth factor homology domains was isolated, suggesting that alternative splicing creates different tie-type receptors. Cells transfected with tie cDNA expression vector produce glycosylated polypeptides of 117 kDa which are reactive to antisera raised against the tie carboxy terminus. The tie gene was located in chromosomal region 1p33 to 1p34. Expression of the tie gene appeared to be restricted in some cell lines; large amounts of tie mRNA were detected in endothelial cell lines and in some myeloid leukemia cell lines with erythroid and megakaryoblastoid characteristics. In addition, mRNA in situ studies further indicated the endothelial expression of the tie gene. The tie receptor tyrosine kinase may have evolved for multiple protein-protein interactions, possibly including cell adhesion to the vascular endothelium.

Diverse receptors for fibroblast growth factors

The development and maintenance of multicellular organisms requires a complex interplay between cells in different tissues. Many of the factors mediating cell-cell communication are polypeptides, which were originally identified because of their ability to stimulate cell growth. In addition to growth signalling several of these factors have been observed to modulate cell survival, chemotaxis and differentiation both in vitro and in vivo. Fibroblast growth factors are a good example of polypeptide mitogens eliciting a wide variety of responses depending on the target cell type. Our knowledge of the cell surface receptors mediating the effects of FGFs has recently expanded remarkably. Perhaps not surprisingly, the complexity of the FGF family and FGF induced responses is reflected as diversity and redundancy of the FGF receptors.

Role of Ets factors in the activity and endothelial cell specificity of the mouse Tie gene promoter

The Tie gene encodes an endothelial cell receptor tyrosine kinase necessary for normal vascular development. The Tie gene promoter targets expression of heterologous genes specifically to endothelial cells in transgenic mice. Here we have characterized the promoter sequences critical for endothelial cell‐specific activity in cultured cells and transgenic mice. Progressive deletions and site‐directed mutations of the promoter showed that the critical endothelial cell‐specific elements are an octamer transcription factor binding site and several Ets binding sites located in two clusters within 300 bp upstream of the major transcription initiation site. Among members of the Ets transcription factor family tested, NERF‐2 (a novel transcription factor related to the ets factor ELF‐1), which is expressed in endothelial cells, and ETS2 showed the strongest transactivation of the Tie promoter; ETS1 gave lower levels of stimulation and the other Ets factors gave little or no transactivation. Furthermore, the Tie promoter directed the production of high amounts of human growth hormone into the circulation of transgenic mice. The secreted amounts correlated with transgene copy number, being relatively insensitive to the effects of the transgene integration site. These properties suggest that Tie promoter activity is controlled by endothelial cell Ets factors and that it has potential for use in vectors for endothelial cell‐specific gene expression.—Iljin, K., Dube, A., Kontusaari, S., Korhonen, J., Lahtinen, I., Oettgen, P., Alitalo, K. Role of Ets factors in the activity and endothelial cell specificity of the mouse Tie gene promoter. FASEB J. 13, 377–386 (1999)

Price integration for domestic and imported sawlogs and pulpwood in Finland: an update

ABSTRACT This paper provides an analysis on the integration of prices for imported coniferous pulpwood and sawlogs, and respective domestic stumpage prices in the Finnish wood market. Eight real price series were investigated during 2002–2014 using monthly observations. The bounds testing approach by Pesaran et al. [(2001) Bounds testing approaches to the analysis of level relationships. J Appl Econom. 16: 289–326. doi:10.1002/jae.616], indicates there are long-run relationships between prices of domestic and imported wood. For more detailed information, the vector error correction model (VECM) approach was used. Estimation of a system with all eight prices with interpretable results did not succeed; therefore, we estimated models for prices of sawlogs and for pulpwood separately. For sawlogs, two co-integrating vectors, one for pine and one for spruce, were found. For pulpwood prices, one co-integrating vector was identified. The estimated VECMs confirm the results of bounds testing approach, suggesting that causation in the Finnish wood market runs from domestic prices to prices of imported wood. We conclude that prices of domestic and imported coniferous logs and pulpwood are closely connected. The question of full integration remains open, as border prices and stumpage prices by definition differ, at least, by logging and transportation costs.