Comparative genomics study reveals Red Sea Bacillus with characteristics associated with potential microbial cell factories (MCFs).

Recent advancements in the use of microbial cells for scalable production of industrial enzymes encourage exploring new environments for efficient microbial cell factories (MCFs). Here, through a comparison study, ten newly sequenced Bacillus species, isolated from the Rabigh Harbor Lagoon on the Red Sea shoreline, were evaluated for their potential use as MCFs. Phylogenetic analysis of 40 representative genomes with phylogenetic relevance, including the ten Red Sea species, showed that the Red Sea species come from several colonization events and are not the result of a single colonization followed by speciation. Moreover, clustering reactions in reconstruct metabolic networks of these Bacillus species revealed that three metabolic clades do not fit the phylogenetic tree, a sign of convergent evolution of the metabolism of these species in response to special environmental adaptation. We further showed Red Sea strains Bacillus paralicheniformis (Bac48) and B. halosaccharovorans (Bac94) had twice as much secreted proteins than the model strain B. subtilis 168. Also, Bac94 was enriched with genes associated with the Tat and Sec protein secretion system and Bac48 has a hybrid PKS/NRPS cluster that is part of a horizontally transferred genomic region. These properties collectively hint towards the potential use of Red Sea Bacillus as efficient protein secreting microbial hosts, and that this characteristic of these strains may be a consequence of the unique ecological features of the isolation environment.

Phylogenetic position of the Drosophila fima and dentissima lineages, and the status of the D. melanogaster species group.

The subgenus Sophophora of Drosophila, which includes D. melanogaster, is an important model for the study of molecular evolution, comparative genomics, and evolutionary developmental biology. Numerous phylogenetic studies have examined species relationships in the well-known melanogaster, obscura, willistoni, and saltans species groups, as well as the relationships among these clades. In contrast, other species groups of Sophophora have been relatively neglected and have not been subjected to molecular phylogenetic analysis. Here, we focus on the endemic African Drosophila fima and dentissima lineages. We find that both these clades fall within the broadly defined melanogaster species group, but are otherwise distantly related to each other. The new phylogeny supports pervasive divergent and convergent evolution of male-specific grasping structures (sex combs). We discuss the implications of these results for defining the boundaries of the melanogaster species group, and weigh the relative merits of "splitting" and "lumping" approaches to the taxonomy of this key model system.

Effects of a saturated layer and recirculation on nitrogen treatment performances of a single stage Vertical Flow Constructed Wetland (VFCW).

Upgrades to enhance nitrogen removal were tested in a 2 year old pilot vertical flow constructed wetland in spring and summer periods. The effects of a saturated layer and of recirculation were tested in particular. Two pilots (L = 2 m, W = 1.25 m, H = 1.2 m), filled with expanded schist (Mayennite(®)), were designed with hydraulic saturated layers of 20 and 40 cm at the bottom. Each pilot was fed with raw domestic wastewater under field conditions according to a hydraulic load of 15-38 cm d(-1) (i.e. 158-401 g COD (chemical oxygen demand) m(-2) d(-1)) and to recirculation rates ranging from 0% up to 150%. The initial load during the first 2 years of operation resulted in an incomplete mineralized accumulated sludge leading to total suspended solids (TSS), COD and biochemical oxygen demand (BOD5) release. A 40 cm hydraulic saturated layer enabled an increase of 5-10% total nitrogen (TN) removal compared to a 20 cm saturated layer. Recirculation allowed the dilution of raw wastewater and enhanced nitrification in a single stage. A design of 1.8 m² pe(-1) (48 cm d(-1), 191 g COD m(-2) d(-1)) with a 40 cm saturated layer and 100% recirculation enabled the French standard D4 (35 mg TSS L(-1), 125 mg COD L(-1), 25 mg BOD5 L(-1)), nitrogen concentrations below 20 mg TKN (total Kjeldahl nitrogen) L(-1) and 50 mg TN L(-1), to be met.

Investigation of the role of sigma1-receptors in inositol 1,4,5-trisphosphate dependent calcium signaling in hepatocytes.

In hepatocytes, as in other cell types, Ca(2+) signaling is subject to complex regulations, which result largely from the intrinsic characteristics of the different inositol 1,4,5-trisphosphate receptor (InsP(3)R) isoforms and from their interactions with other proteins. Although sigma1 receptors (Sig-1Rs) are widely expressed in the liver, their involvement in hepatic Ca(2+) signaling remains unknown. We here report that in this cell type Sig-1R interact with type 1 isoforms of the InsP(3) receptors (InsP(3)R-1). These results obtained by immunoprecipitation experiments are confirmed by the observation that Sig-1R proteins and InsP(3)R-1 colocalize in hepatocytes. However, Sig-1R ligands have no effect on InsP(3)-induced Ca(2+) release in hepatocytes. This can be explained by the rather low expression level expression of InsP(3)R-1. In contrast, we find that Sig-1R ligands can inhibit agonist-induced Ca(2+) signaling via an inhibitory effect on InsP(3) synthesis. We show that this inhibition is due to the stimulation of PKC activity by Sig-1R, resulting in the well-known down-regulation of the signaling pathway responsible for the transduction of the extracellular stimulus into InsP(3) synthesis. The PKC sensitive to Sig-1R activity belongs to the family of conventional PKC, but the precise molecular mechanism of this regulation remains to be elucidated.

[Cutaneous periarteritis nodosa recurring over a period of 30 years in streptococcal infections and progressing toward systemic vasculitis]. / Périartérite noueuse cutanée récidivant depuis 30 ans lors d'infections streptococciques et évoluant vers une vascularite systémique.

INTRODUCTION: Periarteritis nodosa (PAN) is a form of vasculitis affecting the small and medium-sized arteries. Below, we report a case of cutaneous PAN relapsing in streptococcal infections over a period of 30 years and progressing towards systemic vasculitis. CASE REPORT: A 35-year-old man was hospitalised for a retro-pharyngeal access associated with fever, arthralgia, myalgia and inflammatory subcutaneous nodules. Peripheral neurological signs were also seen with deficiency of the elevator muscles in the right foot. Examination of a biopsy from a nodule showed a characteristic image of PAN. Following drainage of the abscess, a favourable outcome was obtained with antibiotics and systemic corticosteroids. History taking showed that the patient had presented similar episodes since the age of 5 years involving arthralgia, myalgia and inflammatory subcutaneous nodules. These episodes appeared to follow a streptococcal infection, of which there was either clinical suspicion or objective elevation of antistreptolysin O (ASLO) titre. Skin biopsy resulted in diagnosis of cutaneous PAN 25 years earlier. In all cases, improvement was achieved by oral corticosteroids combined with treatment of the actual infection. DISCUSSION: In addition to the classic association with hepatitis B, and occasionally hepatitis C, PAN may be associated with streptococcal infections. The cases of post-streptococcal PAN described in the literature are predominantly cutaneous, although it is not rare to find associated arthromyalgia and sensory neurological impairment. We examined three cases of cutaneous PAN with long-term follow-up described in the literature. They began in childhood and the outcome was benign, with no systemic manifestations. Our case differed in terms of the appearance of motor neurological involvement. CONCLUSION: Post-streptococcal PAN of childhood onset generally carries a better prognosis than adult systemic forms. However, our case shows that on rare occasions, there may be very long progression complicated by systemic involvement.

Interactions between globular proteins and procyanidins of different degrees of polymerization.

Interactions of proteins with phenolic compounds occur in food products containing vegetable sources, such as cocoa, cereals, or yogurts containing fruit. Such interactions can modify protein digestion and protein industrial properties. Noncovalent interactions between globular proteins (proteins important in industry) and procyanidins (phenolic compounds present in large quantity in fruits) were studied. The affinity constants between procyanidins of various average degrees of polymerization (DP) and lysozyme or alpha-lactalbumin were measured by isothermal titration calorimetry. The effects of these interactions on protein solubility and foam properties were examined using alpha-lactalbumin and BSA. Weak interactions were found with epicatechin and procyanidin dimers. Procyanidins of n = 5.5 and n = 7.4 showed medium (1.5 x 10(5) M(-1)) and high (8.69 x 10(9) M(-1)) affinities, respectively, for alpha-lactalbumin at pH 5.5, with n the average number of subunits per oligomer. A positive cooperativity of binding at low procyanidin:protein molar ratios was observed. The affinities of alpha-lactalbumin and lysozyme for procyanidins increased when the pH was close to the isoelectric pH. Solubility of lysozyme was strongly decreased by procyanidins of n = 5.5, whereas alpha-lactalbumin and BSA were less affected. Protein solubility in the presence of procyanidins was not affected by increased ionic strength but increased slightly with temperature. Procyanidins of n = 5.5 and n = 7.4 stabilized the average bubble diameter of foam formed with alpha-lactalbumin but had no effect on foam made from BSA. These results indicate that procyanidins of medium can lead to an undesirable decrease of protein solubility, but may play a positive role in foam stability.

Cutaneous events during treatment of chronic inflammatory joint disorders with anti-tumour necrosis factor alpha: a cross-sectional study.

BACKGROUND: Anti-tumour necrosis factors (anti-TNF) are more and more used, but the rate of skin adverse events is not known. OBJECTIVE: The aim was to assess the number of skin infections and other dermatoses in patients treated with anti-TNFalpha. PATIENTS AND METHODS: One hundred eighty-seven patients suffering from rheumatoid arthritis or ankylosing spondylitis underwent a dermatological exam. Patients with anti-TNF were compared with those without this treatment in a prospective transversal study. RESULTS: Among them, 59 patients were treated with anti-TNFalpha and steroids were prescribed in 100 cases. There was no difference in the prevalence of skin infections or eczema or tumours. Skin drug reactions were observed in six patients. Infections by dermatophytes appear very frequent, approaching 70% in both groups. CONCLUSIONS: This study shows that skin infections (or other skin diseases) are not more frequent in these patients. No differences were observed in infections (bacterial fungal, parasital or viral), tumours, psoriasis or the manifestations of atopic dermatitis. Nonetheless, a long-term survey might be interesting, especially about skin tumours.

Effects of the prostaglandins PGF2alpha and PGE2 on calcium signaling in rat hepatocyte doublets.

Coordination of intercellular Ca2+ signals is important for certain hepatic functions including biliary flow and glucose output. Prostaglandins, such as PGF2alpha and PGE2, may modify these hepatocyte functions by inducing Ca2+ increase, but very little is known about the organization of the Ca2+ signals induced by these agonists. We studied Ca2+ signals induced by PGF2alpha and PGE2 in fura-2 AM-loaded hepatocyte doublets. Even though both prostaglandins induced Ca2+ oscillations, neither PGF2alpha nor PGE2 induced coordinated Ca2+ oscillations in hepatocyte doublets. Gap junction permeability (GJP), assessed by fluorescence recovery after photobleaching, showed that this absence of coordination was not related to a defect in GJP. Inositol (1,4,5)trisphosphate [Ins(1,4,5)P3] assays and the increase in Ins(1,4,5)P3 receptor sensitivity to Ins(1,4,5)P3 observed in response to thimerosal suggested that the absence of coordination was a consequence of the very small quantity of Ins(1,4,5)P3 formed by these prostaglandins. Furthermore, when PGE2 and PGF2alpha were added just before norepinephrine, they favored the coordination of Ca2+ signals induced by norepinephrine. However, GJP between hepatocyte doublets was strongly inhibited by prolonged (>or=2 h) treatment with PGF2alpha, thereby preventing the coordination of Ca2+ oscillations induced by norepinephrine in these cells. Thus, depending on the time window, prostaglandins, specially PGF2alpha, may enhance or diminish the propagation of Ca2+ signals. They may therefore contribute to the fine tuning of Ca2+ wave-dependent functions, such as nerve stimulation, hormonal regulation of liver metabolism, or bile secretion, in both normal and pathogenic conditions.

Chimeric VEGFRs are activated by a small-molecule dimerizer and mediate downstream signalling cascades in endothelial cells.

Despite much interest in vascular endothelial growth factor (VEGF) and its receptors (VEGFRs -1 and -2), VEGF-induced signalling cascades remain incompletely defined. Attempts to assign individual responses to a particular receptor have used either transfected cell lines, receptor-specific growth factors or antisense oligonucleotides. Such studies have attributed the majority of VEGF-induced responses to activation of VEGFR-2. As a consequence of poor growth factor-induced VEGFR-1 autophosphorylation however, observations from these studies may instead reflect the relative activation of the two receptors. We have generated novel chimeric VEGF receptors in which the dimerization domain of the B subunit of DNA gyrase is fused to the cytoplasmic domain of VEGFRs -1 and -2. When expressed in porcine aortic endothelial cells, both chimeric VEGFR-1 and -2 autophosphorylate in response to addition of the small-molecule dimerizing agent, coumermycin. Once activated, both receptors induce downstream signalling cascades, exemplified here by the activation of MAPK, PLCgamma and PKB/Akt. Furthermore, we demonstrate that the Y1175 residue of VEGFR-2 is essential for the activation of PLCgamma mediated by this chimeric receptor. In contrast to previous reports which show a limited ability of VEGFR-1 to mediate signalling cascades, we show that once sufficiently activated, VEGFR-1 signals in a similar manner to VEGFR-2 in endothelial cells.

Modulation of signal-transduction pathways by chemopreventive agents.

For a disease such as cancer, where a number of alterations to normal cell function accumulate over time, there are several opportunities to inhibit, slow down or even reverse the process. Many of the changes which drive the disease process occur in cell-signalling pathways that regulate proliferation and apoptosis. As our knowledge of these complicated signalling networks improves, it is becoming clear that many molecules, both drugs and naturally occurring dietary constituents, can interact beneficially with deregulated pathways. Aspirin and other non-steroidal anti-inflammatory drugs, as well as natural compounds present in plants such as green vegetables and tea, can modulate signalling by affecting kinase activity and therefore phosphorylation of key molecules. Examples of pathways which can be modulated by these agents include activation of the transcription factor nuclear factor kappaB by tumour promoters or cytokines, signalling by growth factors through the growth-factor receptor/extracellular-regulated protein kinase pathways and by a number of other molecules through the stress-activated c-Jun N-terminal kinase and p38 pathways. These mitogen-activated protein kinase pathways regulate a number of transcription factors including c-Fos and c-Jun. Evidence exists, at least from in vitro experiments, that by targeting such pathways, certain dietary compounds may be able to restore abnormal rates of apoptosis and proliferation to more normal levels.

The Shc-related adaptor protein, Sck, forms a complex with the vascular-endothelial-growth-factor receptor KDR in transfected cells.

Despite much progress in recent years, the precise signalling events triggered by the vascular-endothelial-growth-factor (VEGF) receptors, fms-like tyrosine kinase (Flt1) and kinase insert domain-containing receptor (KDR), are incompletely defined. Results obtained when Flt1 and KDR are individually expressed in fibroblasts or porcine aortic endothelial cells have not been entirely consistent with those observed in other endothelial cells expressing both receptors endogenously. It has also been difficult to demonstrate VEGF-induced phosphorylation of Flt1, which has led to speculation that KDR may be the more important receptor for the mitogenic action of VEGF on endothelial cells. In an attempt to identify physiologically important effectors which bind to KDR, we have screened a yeast two-hybrid mouse embryo library with the cytoplasmic domain of KDR. Here we describe the identification of the adaptor protein, Shc-like protein (Sck), as a binding partner for KDR. We demonstrate that this interaction requires phosphorylation of KDR, and identify the binding site for the Src-homology 2 (SH2) domain as tyrosine-1175 of KDR. We have also shown that the SH2 domain of Sck, but not that of Src-homology collagen protein (Shc), can precipitate phosphorylated KDR from VEGF-stimulated porcine aortic endothelial cells expressing KDR, and that an N-terminally truncated Sck protein can associate with KDR, in a phosphorylation-dependent fashion, when co-expressed in human embryonic kidney 293 cells. Furthermore, we demonstrate that in the two-hybrid assay, both Shc and Sck SH2 domains can associate with the related receptor Flt1.

Blocking and suppressing mechanisms of chemoprevention by dietary constituents.

Many dietary constituents are chemopreventive in animal models, and experiments with cultured cells are revealing various potential mechanisms of action. Compounds classified as blocking agents can prevent, or greatly reduce, initiation of carcinogenesis, while suppressing agents affect later stages of the process by reducing cell proliferation. Many compounds have both types of activity. Blocking mechanisms include alteration of drug metabolising activities and scavenging of reactive oxygen species. Mechanisms which suppress tumorigenesis often involve modulation of signal transduction pathways, leading to altered gene expression, cell cycle arrest or apoptosis. As our knowledge of how these dietary components affect cell biochemistry improves, so the likelihood of success in chemoprevention trials and in provision of dietary advice to the general population to optimise the chances of preventing disease is increased.

Microinjection of anti-p21 antibodies induces senescent Hs68 human fibroblasts to synthesize DNA but not to divide.

Replicative senescence is characterized by irreversible growth arrest and has been defined by four genetic complementation groups. One of these groups is associated with the predominance of underphosphorylated, growth-suppressive retinoblastoma tumor suppressor protein (pRb). Although certain members of the cyclin-dependent kinase (cdk)/cyclin family, some of which phosphorylate pRb, are underexpressed in senescent cells, others are expressed but inactive. This lack of cdk activity and arrest in the G1 phase of the cell cycle is likely attributable to the induction upon senescence of the G1-S cdk/cyclin inhibitors p21 (WAF1/CIP1/Sdi) and p16INK4. In fact, in early presenescent normal diploid fibroblasts in which p21 is inactivated, senescence is bypassed or postponed. Moreover, in senescent cells in which p53 function was inhibited, DNA synthesis was reinitiated, an effect likely attributable, in part, to the dependence of p21 expression on p53. We report here that the apparent inactivation of p21 in senescent human fibroblasts through the introduction of inhibitory alpha-p21 antibodies causes these cells to reenter the S-phase of the cell cycle. The disruption of p21 activity affects the p21-Rb-E2F pathway in that the expression of genes transcriptionally regulated by E2F, such as cyclin A and cdc2, were found to be up-regulated in injected cells. No evidence of cell division was observed. This suggests that p21 plays an important role in the maintenance of senescence and in the inhibition of S-phase progression, but inhibition of p21 activity is insufficient to permit cells to complete the cell cycle.

Talin contains three similar vinculin-binding sites predicted to form an amphipathic helix.

Using recombinant talin polypeptides and an SDS/PAGE-blot overlay assay, we have previously identified three regions of talin that are involved in binding to vinculin [Gilmore, Wood, Ohanian, Jackson, Patel, Rees, Hynes and Critchley (1993) J. Cell Biol. 122, 337-347]. We have confirmed these observations by using a yeast two-hybrid assay and shown that talin residues 498-656, 852-950 and 1929-2029 are each capable of binding to vinculin residues 1-258. We have further defined the three vinculin-binding sites in talin to residues 607-636, 852-876 and 1944-1969; alignment of these sequences shows 59% similarity, although there are only two identical residues. Predictions of secondary structure indicate that this vinculin-binding motif forms an amphipathic alpha-helix. The hydrophobic face of helix 607-636 contains three aligned leucines (residues 608, 615 and 622), which show conservative substitutions in the other two sites. To test the possibility that this might constitute a leucine zipper involved in vinculin binding, we mutated each leucine residue to an alanine. The results showed that this leucine repeat is not essential to the interaction between talin and vinculin. We also used the yeast two-hybrid system to define further the talin-binding site within vinculin residues 1-258. C-terminal deletions made in accordance with exon boundaries showed that vinculin residues 1-167 are capable of interacting with each of the three vinculin-binding sites in talin. However, all N-terminal deletions abolished binding. The results suggest that the talin-binding site in vinculin has a relatively complex fold, whereas the vinculin-binding motif in talin is contained within a short linear peptide sequence that is repeated three times in the talin rod domain.

The proapoptotic effect of hepatitis B virus HBx protein correlates with its transactivation activity in stably transfected cell lines.

The role of hepatitis B virus HBx protein in the carcinogenesis associated with chronic viral infection remains ill-defined. Indeed, pleiotropic effects have been ascribed to HBx: in addition to its well-documented ability to indirectly stimulate transcription, the protein has been reported to affect cell growth, signal transduction, DNA repair and apoptosis. In this work, we generated Chang (CCL-13)-derived cell lines constitutively expressing wild type or mutant HBx, as a model of HBx-host cell interaction closer to the chronic infection setting, than the classically used transient expression systems. We document the potentiation by HBx of the apoptotic cell death pathway in the recipient cells. This effect is unlikely to rely on p53 activity since the protein is functionally inactivated in CCL-13. In addition, antioxidants and cyclosporin A failed to reduce the apoptotic response back to the normal level, suggesting that production of reactive oxygen species and calcineurin activation are not directly involved in the proapoptotic effect of HBx. In contrast, our data show that transactivation and stimulation of apoptosis are tightly linked HBx activities. Finally, expression of transactivation-active protein did not result in detectable change in the pattern of MAP kinases phosphorylation nor did it affect the ability of the host cell to repair in vitro irradiated plasmid DNA.

Identification of three distinct regions of allelic deletions on the short arm of chromosome 8 in hepatocellular carcinoma.

The chromosome 8p is associated with a large number of allelic imbalances in epithelial tumors including hepatocellular carcinoma (HCC). However, no tumor suppressor gene has been identified so far in this particular region of the genome. To further clarify the pattern of allelic deletions on chromosome 8p in HCC, we have undertaken high-density polymorphic marker analysis of 109 paired normal and primary tumor samples using 40 microsatellites positioned every 2 cm in average throughout 8p. We found that 60% of the tumors exhibited loss of heterozygosity (LOH) at one or more loci at 8p with three distinct minimal deleted areas: a 13 cm region in the distal part of 8p21, a 9 cm area in the more proximal portion of 8p22 and a 5 cm area in 8p23. These data strongly suggest the presence of at least three novel tumor suppressor loci on 8p in hepatocellular carcinoma.

Metabolic evolution in alpha-amylases from Drosophila virilis and D. repleta, two species with different ecological niches.

alpha-Amylases from Drosophila virilis and D. repleta were partially purified by ion exchange chromatography. The two amylases share common characteristics for pH and cations effects, although with slight differences. D. virilis has optimal activity at pH 6.6 and D. repleta at pH 7.2. Calcium, sodium, and potassium cations activate amylolytic activity in both species but Ba2+ has an activation effect in D. repleta only. In contrast, there are major differences in thermal offbility and kinetics among amylases of the two species. D. virilis amylase is much more stable at high temperature and the optimal temperatures are very different between the two species, respectively, 45 degrees C and 30 degrees C for D. virilis and D. repleta. alpha-Amylase activity using different substrates is greater on starch than on glycogen in both species and still higher on amylose for D. virilis, the nonfungus feeder species. alpha-Amylase of D. repleta, the mycophagous species, has a better affinity to amylopectin and glycogen. Such differences in substrate specificity suggest adaptation to different resources in these species living in different habitats. Metabolic evolution seems to have occurred through a "tradeoff" between kinetic effectiveness and the nature of substrate, with a higher Vmax on amylose for D. virilis and a lower K(m) on glycogen for D. repleta.

Interaction of the UV-damaged DNA-binding protein with hepatitis B virus X protein is conserved among mammalian hepadnaviruses and restricted to transactivation-proficient X-insertion mutants.

We carried out a comparative analysis of several proposed host protein partners of the human hepatitis B virus X protein (HBx) using both the GAL4- and the LexA-based yeast two-hybrid system. We showed that the interaction of HBx with the UV-damaged DNA-binding protein (UVDDB) is positive in both yeast systems, detectable in cotransfected human cells, conserved by rodent hepadnavirus X proteins (known to transactivate in human cells), and tightly correlated with the transactivation proficiency of X-insertion mutants. Taken together, our results strongly suggest that UVDDB is involved in X-mediated transactivation.

Identification of ErbB3-stimulated genes using modified representational difference analysis.

The epidermal growth factor receptor (EGFR) family of tyrosine kinases is involved in the growth of normal and tumour cells. The specific contribution of each of the four family members to these processes remains unclear. In the present study we have used a PCR-based subtractive approach to identify differences in messages induced in response to activation of ErbB3 and EGFR. The approach described is a modification of the representational difference analysis technique adapted for analysis of cDNA, which we have modified to permit identification of differential gene expression using as little as 20 microg of total RNA as the starting material. The mRNA obtained from EGF-stimulated NIH-3T3 cells expressing chimaeric EGFR-ErbB3 receptors provided the tester amplicons (small PCR-amplified fragments) which were subtracted against driver amplicons derived from unstimulated NIH-3T3 cells expressing the EGFR-ErbB3 chimaera or EGF-stimulated NIH-3T3 cells overexpressing the EGFR. A total of 22 different clones were isolated, 90% of which showed increased expression in the tester amplicons. Six of these, corresponding to known DNA sequences, were selected for further Northern blot analysis against total RNA prepared from the starting cell lines. Of these, the gene encoding the protein dlk (or a closely related protein, Pref-1) was identified as being regulated by ErbB3 but not by the EGFR. Other genes appeared to be elevated by both ErbB3 and EGFR, including those encoding c-jun, Ret finger protein (RFP), neuroleukin and amyloid protein precursor. One gene product, TIS11, was identified as being regulated by EGFR but not by ErbB3.