Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A gene encoding a novel type of receptor protein-tyrosine kinase was identified in Hydra vulgaris. The extracellular portion of this receptor (which we have named Sweet Tooth) contains four C-type lectin-like domains (CTLDs). Comparison of the sequences of these domains with the sequences of the carbohydrate recognition domains of various vertebrate C-type lectins shows that Sweet Tooth CTLD1 and CTLD4 have amino acids in common with those shown to be involved in carbohydrate binding by the lectins. Comparison of sequences encoding CTLD1 from the Sweet Tooth genes from different species of Hydra shows variation in some of the conserved residues that participate in carbohydrate binding in C-type lectins. The Sweet Tooth gene is expressed widely in the Hydra polyp, and expression is particularly high in the endoderm of the tentacles. Treatment of polyps with peptides corresponding to sequences in the Sweet Tooth CTLDs results in the disintegration of the animal. These same peptides do not block adhesion or morphogenesis of Hydra cell aggregates.
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PMID:Sweet Tooth, a novel receptor protein-tyrosine kinase with C-type lectin-like extracellular domains. 1074 20

Recent evidence indicates that STAT proteins can be activated by a variety of receptor and non-receptor protein-tyrosine kinases. Unlike cytokine-induced activation of STATs, where JAKs are known to play a pivotal role in phosphorylating STATs, the mechanism for receptor protein-tyrosine kinase-mediated activation of STATs remains elusive. In this study, we investigated the activation of STAT proteins by the insulin-like growth factor I receptor (IGF-IR) in vitro and in vivo and assessed the role of JAKs in the process of activation. We found that STAT3, but not STAT5, was activated in response to IGF-I in 293T cells cotransfected with IGF-IR and STAT expression vectors. Moreover, tyrosine phosphorylation of STAT3, JAK1, and JAK2 was increased upon IGF-I stimulation of endogenous IGF-IR in 293T cells transfected with the respective STAT or JAK expression vector. Supporting the observation in 293T cells, endogenous STAT3 was tyrosine-phosphorylated upon IGF-I stimulation in the muscle cell line C2C12 as well as in various embryonic and adult mouse organs during different stages of development. Dominant-negative JAK1 or JAK2 was able to block the IGF-IR-mediated tyrosine phosphorylation of STAT3 in 293T cells. A newly identified family of proteins called SOCS (suppressor of cytokine signaling), including SOCS1, SOCS2, SOCS3 and CIS, was able to inhibit the IGF-I-induced STAT3 activation as well with varying degrees of potency, in which SOCS1 and SOCS3 appeared to have the higher inhibitory ability. Inhibition of STAT3 activation by SOCS could be overcome by overexpression of native JAK1 and JAK2. We conclude that IGF-I/IGF-IR is able to mediate activation of STAT3 in vitro and in vivo and that JAKs are essential for the process of activation.
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PMID:Mechanism of STAT3 activation by insulin-like growth factor I receptor. 1074 72

Axial patterning of the aboral end of the hydra body column was examined using expression data from two genes. One, shin guard, is a novel receptor protein-tyrosine kinase gene expressed in the ectoderm of the peduncle, the end of the body column adjacent to the basal disk. The other gene, manacle, is a paired-like homeobox gene expressed in differentiating basal disk ectoderm. During regeneration of the aboral end, expression of manacle precedes that of shin guard. This result is consistent with a requirement for induction of peduncle tissue by basal disk tissue. Our data contrast with data on regeneration of the oral end. During oral end regeneration, markers for tissue of the tentacles, which lie below the extreme oral end (the hypostome), are detected first. Later, markers for the hypostome itself appear at the regenerating tip, with tentacle markers displaced to the region below. Additional evidence that tissue can form basal disk without passing through a stage as peduncle tissue comes from LiCl-induced formation of patches of ectopic basal disk tissue. While manacle is ectopically expressed during formation of basal disk patches, shin guard is not. The genes examined also provide new information on development of the aboral end in buds. Although adult hydra are radially symmetrical, expression of both genes in the bud's aboral end is initially asymmetrical, appearing first on the side of the bud closest to the parent's basal disk. The asymmetry can be explained by differences in positional information in the body column tissue that evaginates to form a bud. As predicted by this hypothesis, grafts reversing the orientation of evaginating body column tissue also reverse the orientation of asymmetrical gene expression.
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PMID:Expression of a novel receptor tyrosine kinase gene and a paired-like homeobox gene provides evidence of differences in patterning at the oral and aboral ends of hydra. 1075 14

In a screen for receptor protein-tyrosine kinase (RTK) genes expressed during gametogenesis in the cnidarian Hydra vulgaris, we isolated a cDNA encoding Lemon, an RTK with unusual features. Lemon is orthologous to Drosophila Dtrk, chicken Klg, and human colon carcinoma kinase-4. These genes constitute an RTK class characterized by a conserved transmembrane sequence, the presence of extracellular immunoglobulin-like repeats, and the absence of the DFG motif in the kinase domain. We provide evidence that Lemon is a component of an unusual RTK signal transduction mechanism that may involve transmembrane domain-mediated interactions and may not be dependent on its own catalytic activity. Lemon transcription is dynamically regulated in interstitial cells during asexual budding and gametogenesis. Transcriptional up-regulation occurs early in spermatogenesis and oogenesis concurrent with the local accumulation of interstitial cells in the body column of sexual polyps.
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PMID:Lemon encodes an unusual receptor protein-tyrosine kinase expressed during gametogenesis in Hydra. 1092 67

The focal adhesion (FAK) non-receptor protein-tyrosine kinase (PTK) links both extracellular matrix/integrin and growth factor stimulation to intracellular signals promoting cell migration. Here we show that both transient and stable overexpression of the FAK C-terminal domain termed FRNK (FAK-related non-kinase) inhibits serum and platelet-derived growth factor (PDGF)-BB-induced vascular smooth muscle cell (SMC) migration in wound healing and in vitro Boyden Chamber chemotaxis assays, respectively. Expression of FRNK, but not a point mutant of FRNK (FRNK L1034S), disrupted the formation of a complex containing both FAK and the activated PDGF-beta receptor and resulted in reduced tyrosine phosphorylation of endogenous FAK at the Tyr-397 binding site for Src family PTKs. As demonstrated using FAK-deficient and FAK-reconstituted fibroblasts, FAK positively contributed to PDGF-BB-stimulated ERK2/MAP kinase activity, and in SMCs, ERK2/MAP kinase activity was required for PDGF-BB-stimulated chemotaxis. Stable expression of FRNK but not FRNK L1034S expression in SMCs lowered the extent and duration of stimulated ERK2/MAP kinase activation at low but not at high PDGF-BB concentrations. Importantly, stable expression of FRNK in SMCs did not affect SMC morphology or proliferation in culture. Because the increased migration of vascular SMCs in response to extracellular matrix proteins and growth factors contributes to neointima formation, our results show that FAK inhibition by FRNK expression may provide a novel approach to regulate abnormal vascular SMC migration in vivo.
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PMID:Focal adhesion kinase facilitates platelet-derived growth factor-BB-stimulated ERK2 activation required for chemotaxis migration of vascular smooth muscle cells. 1099 18

We developed a system to study the function of the ectodomain of RPTPalpha, a transmembrane protein-tyrosine phosphatase, by fusing the HA-epitope tagged ectodomain of RPTPalpha to the transmembrane and intracellular domain of the epidermal growth factor receptor, EGFR, a receptor protein-tyrosine kinase that is activated by dimerization. Although the use of chemical crosslinkers shows that preformed HARPTPalpha-EGFR dimers exist, bivalent anti-HA-tag antibody activated HARPTPalpha-EGFR chimeras, suggesting this system may be used to study regulation of dimerization. We used this system to show that newborn calf serum may contain (a) potential ligand(s) for RPTPalpha. Our results suggest that RPTPalpha dimerization and thus activity may be affected by ligand binding.
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PMID:Antibody-induced dimerization of HARPTPalpha-EGFR chimera suggests a ligand dependent mechanism of regulation for RPTPalpha. 1107 85

The mechanisms by which most receptor protein-tyrosine kinases (RTKs) transmit signals are now well established. Binding of ligand results in the dimerization of receptor monomers followed by transphosphorylation of tyrosine residues within the cytoplasmic domains of the receptors. This tidy picture has, however, some strange characters lurking around the edges. Cases have now been identified in which RTKs lack kinase activity, but, despite being "dead" appear to have roles in signal transduction. Even stranger are the cases in which genes encoding RTKs produce protein products consisting of only a portion of the kinase domain. At least one such "fractured" RTK appears to be involved in signal transduction. Here we describe how these strange molecules might function and discuss the questions associated with their evolution. BioEssays 23:69-76, 2001.
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PMID:Deceiving appearances: signaling by "dead" and "fractured" receptor protein-tyrosine kinases. 1113 11

EphB2, a member of the Eph receptor protein-tyrosine kinase family, is overexpressed in several human gastrointestinal tumors. Furthermore, the EphB2 gene is localized at 1p35-p36.1, a frequently deleted region in colon and other cancers. So, despite its overexpression in some kind of tumors, we decided to study the possibility of involvement in the EphB2 gene (EPHB2) mutation in colon cancers, because some of the well known tumor suppressor genes (e.g. p53) is overexpressed (really accumulated) in tumors. Fifty colon tumor samples of matched with their respective normal tissues, were studied for mutation of the EPHB2. Analysis of the genomic structure of EphB2 and survey of all 16 exons revealed an infrequent polymorphism (intron 2) and mutation (intron 8). Another polymorphism in exon 6, localized at nucleotide 1359 (A-->G) was found to be rather frequent in Japanese and Chinese subjects, but very rare in Caucasians. Taking advantage of this polymorphism within EPHB2, we surveyed the loss of heterozygosity (LOH) status of this gene in Japanese colorectal tumors. Among the 50 samples analyzed, 24 were informative, and LOH was found in five of the15 (33.3%) informative rectal cancer cases. Mutation analysis covering all 16 exons in the remaining allele did not reveal any mutations. Thus, EPHB2 is not a classical tumor suppressor gene.
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PMID:Genomic structure and loss of heterozygosity of EPHB2 in colorectal cancer. 1116 21

A search of databases with the sequence from the 5' untranslated region of a Hydra cDNA clone encoding a receptor protein-tyrosine kinase revealed that a number of Hydra cDNAs contain one of two different sequences at their 5' ends. This finding suggested the possibility that mRNAs in Hydra receive leader sequences by trans-splicing. This hypothesis was confirmed by the finding that the leader sequences are transcribed as parts of small RNAs encoded by genes located in the 5S rRNA clusters of Hydra. The two spliced leader (SL) RNAs (SL-A and -B) contain splice donor dinucleotides at the predicted positions, and genes that receive SLs contain splice acceptor dinucleotides at the predicted positions. Both of the SL RNAs are bound by antibody against trimethylguanosine, suggesting that they contain a trimethylguanosine cap. The predicted secondary structures of the Hydra SL RNAs show significant differences from the structures predicted for the SLs of other organisms. Messenger RNAs have been identified that can receive either SL-A or -B, although the impact of the two different SLs on the function of the mRNA is unknown. The presence and features of SL addition in the phylum Cnidaria raise interesting questions regarding the evolution of this process.
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PMID:Trans-spliced leader addition to mRNAs in a cnidarian. 1133 66

Fps/Fes and Fer are the only known members of a distinct subfamily of the non-receptor protein-tyrosine kinase family. Recent studies indicate that these kinases have roles in regulating cytoskeletal rearrangements and inside out signalling that accompany receptor ligand, cell matrix and cell cell interactions. Genetic analysis using transgenic mouse models also implicates these kinases in the regulation of inflammation and innate immunity.
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PMID:Closing in on the biological functions of Fps/Fes and Fer. 1199 47


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