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From a subtracted cDNA library we have isolated a cDNA clone coding for a novel transformation-sensitive protein which is expressed by human fibroblasts, but not by their matched SV40 transformed counterparts. This protein has a molecular mass of 51 kDa and is highly related to the HtrA family of serine proteases from bacteria. At the N-terminal end, it contains an IGF-binding domain which may modulate the activity of the associated serine protease. Our data are consistent with the assumption that the novel protein represents one of the proteases that regulate the availability of IGFs by cleaving IGFbinding proteins.

Focal adhesions are essential cellular structures of metazoan organisms that link the extracellular matrix to the cytoskeleton. The controlled assembly and disassembly of focal adhesions is critical for a diversity of biological functions, including cell adhesion, motility, and spreading. Typically, focal adhesions are found at sites where a number of proteins from different signaling pathways converge to respond to extracellular signals (1). Thus far, more than 50 different focal adhesion proteins have been identified (2). Among them are several adapter proteins with protein-protein interaction motifs that play an important role in the dynamic assembly of focal adhesions.One of these adapter proteins is zyxin. Zyxin was originally identified in chicken fibroblasts as a protein associated with stress fibers and focal adhesions (3). The mammalian homologue of avian zyxin was subsequently cloned from a subtracted cDNA library enriched with clones that are down-regulated in transformed fibroblasts (4). At the same time, human zyxin was also cloned from umbilical vein endothelial cells by crosshybridization (5). Analysis of the protein sequence revealed the typical structure of a multidomain protein. At the C terminus, zyxin contains three LIM domains arranged in tandem. LIM domains are cysteine-rich motifs with two zinc finger-like structures that mediate specific protein-protein interactions. Three different binding partners for the LIM domains of zyxin have been identified, namely, the cysteine-rich protein CRP, the adapter protein p130cas, and the tumor suppressor protein H-warts/LATS1 (6 -8). At the N terminus, zyxin features an extended, proline-rich domain, which contains a nuclear export signal and several proline clusters. By virtue of these proline clusters, zyxin binds to proteins of the Ena/VASP family, which control the assembly and disassembly of actin filaments (9). The proline clusters also serve as docking sites for the oncoprotein Vav, a nucleotide exchange factor for the Rho family of GTPases (10). Moreover, the extended N-terminal domain is responsible for the interaction of zyxin with the actin-bundling protein ␣-actinin (11). We have recently demonstrated that a linear sequence motif found at the extreme N terminus of zyxin is essential for this interaction (12, 13). Our observation is supported by the fact that LPP (lipoma preferred partner), another member of the zyxin family containing the same linear motif, binds to ␣-actinin, too (14).Several pieces of evidence from different lines of investigation suggest that zyxin might play an important role in the organization of the actin cytoskeleton. Zyxin induces the polymerization of actin on the surface of mitochondria when artificially targeted to these ectopic sites (15,16). Actin polymerization and the resulting tension appear to be crucial for the dynamic assembly of focal adhesions (1). On the other hand, zyxin is one of the first molecules that dissociate from dissolving focal adhesions (17). This observation raises the intriguing possibil...

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FGFRL1 (fibroblast growth factor receptor like 1) is the most recently discovered member of the FGFR family. It contains three extracellular Ig-like domains similar to the classical FGFRs, but it lacks the protein tyrosine kinase domain and instead contains a short intracellular tail with a peculiar histidine-rich motif. The gene for FGFRL1 is found in all metazoans from sea anemone to mammals. FGFRL1 binds to FGF ligands and heparin with high affinity. It exerts a negative effect on cell proliferation, but a positive effect on cell differentiation. Mice with a targeted deletion of the Fgfrl1 gene die perinatally due to alterations in their diaphragm. These mice also show bilateral kidney agenesis, suggesting an essential role for Fgfrl1 in kidney development. A human patient with a frameshift mutation exhibits craniosynostosis, arguing for an additional role of FGFRL1 during bone formation. FGFRL1 contributes to the complexity of the FGF signaling system.