Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.10.2 (focal adhesion kinase)
44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protein tyrosine phosphorylation has been hypothesized to play a key role in the growth signaling induced by erythropoietin (Epo), although the Epo receptor (EpoR), a member of the cytokine receptor superfamily, lacks a tyrosine kinase domain. Recently, the JAK2 tyrosine kinase was shown to be activated on Epo stimulation and to bind to the cytoplasmic domain of EpoR in vitro. To further explore the mechanisms of activation of JAK2 in EpoR-mediated signal transduction, we assessed the conditions for association of JAK2 with EpoR in vivo. Epo stimulation rapidly induced association of JAK2 with the EpoR in an interleukin 3 (IL-3)-dependent cell line transfected with the wild-type EpoR. On Epo stimulation JAK2 also associated with a truncated mutant EpoR (H-mutant), which is mitogenetically active but not tyrosine phosphorylated, indicating that association does not require receptor phosphorylation and occurs in the membrane proximal region. However, association was not detected with mutant receptors inactivated by an internal deletion or a point mutation, Trp282 to Arg, in a membrane-proximal cytoplasmic region (PB or PM4 mutant, respectively). Immune complex kinase assays of anti-EpoR immunoprecipitates also revealed that activated JAK2 associates with the EpoR in Epo-stimulated cells. By this approach, association also occurred with the mitogenically active H mutant but not with the mitogenically inactive PB or PM4 mutants. In the immune complex kinases assays, EpoR, JAK2, and a 150-kD protein were phosphorylated on tyrosine. Taken together, the results further support the hypothesis that, on Epo stimulation, JAK2 associates with the membrane-proximal cytoplasmic region of the EpoR to be activated and induces tyrosine phosphorylation of cellular substrates, including the EpoR, to transduce a growth signal.
...
PMID:Erythropoietin induces association of the JAK2 protein tyrosine kinase with the erythropoietin receptor in vivo. 806 43

The interleukin 6 receptor-associated signal transducer, gp130, is shared by receptor complexes for leukemia inhibitory factor, oncostatin M, ciliary neurotrophic factor, and interleukin 11. We show here that JAK2 kinase is rapidly tyrosine phosphorylated in mouse embryonic stem cells whose pluripotentiality is maintained only by gp130-sharing cytokines after stimulation that is known to induce gp130 homodimerization. JAK1 is also tyrosine phosphorylated, but to a lesser extent, under the same conditions. Comparable results are obtained with hemopoietic lineage cells such as myeloid leukemic M1 cells and pro-B-cell line-derived transfectants expressing gp130, the former of which differentiate into macrophages after stimulation of gp130 and the latter of which initiate DNA synthesis. gp130-dimerizing stimulus upregulates kinase activity of JAK2 as revealed by immunocomplex kinase assay. Deletion or point mutation in the membrane-proximal cytoplasmic motifs in gp130 that are conserved in the hemopoietic cytokine receptor family results in the loss of tyrosine phosphorylation of JAK2, which coincides with the lack of signal transducing capability of gp130 mutants.
...
PMID:Activation of JAK2 kinase mediated by the interleukin 6 signal transducer gp130. 813 89

The erythropoietin receptor (EPO-R), a member of the cytokine receptor superfamily, can be activated to signal cell growth by binding either EPO or F-gp55, the Friend spleen focus-forming virus glycoprotein. Activation by F-gp55 results in constitutive EPO-R signalling and the first stage of Friend virus-induced erythroleukemia. We have generated a truncated form of the EPO-R polypeptide [EPO-R(T)] which lacks the critical cytoplasmic signal-transducing domain of the EPO-R required for EPO- or F-gp55-induced cell growth. EPO-R(T) specifically inhibited the EPO-dependent growth of EPO-R-expressing Ba/F3 cells without changing the interleukin-3-dependent growth of these cells. In addition, Ba/F3 cells that coexpressed wild-type EPO-R and EPO-R(T) were resistant to transformation by F-gp55 despite efficient expression of the F-gp55 transforming oncoprotein in infected cells. EPO-R(T) inhibited the EPO-dependent tyrosine phosphorylation of wild-type EPO-R, the tyrosine kinase (JAK2), and the SH2 adaptor protein (Shc). In conclusion, the EPO-R(T) polypeptide is a dominant negative polypeptide which specifically interferes with the early stages of EPO-R-mediated signal transduction and which prevents Friend virus transformation of erythroblasts.
...
PMID:A dominant negative erythropoietin (EPO) receptor inhibits EPO-dependent growth and blocks F-gp55-dependent transformation. 813 31

We have cloned and sequenced a cDNA (JAK3) encoding a novel member of the JAK family of protein tyrosine kinases. JAK3 was identified by RT-PCR of rat mesangial cells using degenerate oligonucleotide primers, and a full-length clone was isolated from a rat spleen cDNA library. The primary structure of JAK3 showed cDNA with an open reading frame of 1,100 amino acids which comprises the PTK catalytic domain and a second kinase-related domain characteristic for JAK kinase. JAK3 was phylogenetically shown to be most closely related to JAK2 among the previously known JAK family members, JAK1, JAK2 and Tyk2. Southern analysis revealed that JAK3 is a single copy gene and well conserved in the vertebral genome. Northern analysis indicated that the 4.0 kb mRNA was transcribed in a variety of tissues including spleen, lung, kidney and intestine.
...
PMID:Molecular cloning of rat JAK3, a novel member of the JAK family of protein tyrosine kinases. 814 63

Interleukin-11 (IL-11) shares the common signal transducer gp130 with IL-6, leukemia inhibitory factor (LIF), and oncostatin M (OSM) and triggers activation of unknown tyrosine kinases as the early steps of signal transduction pathway. Here we identify a 130-kilodalton tyrosine-phosphorylated protein induced by IL-11 in 3T3-L1 cells as JAK2 tyrosine kinase. We further show that the in vitro kinase activity of JAK2 is greatly enhanced following stimulation with IL-11 in 3T3-L1 cells and TF-1 cells. Furthermore, we demonstrate that JAK2 physically associates with the signal transducer gp130. Similar results were observed following stimulation with IL-6, LIF, and OSM. However, we were unable to show that JAK1 is tyrosine phosphorylated and activated by IL-11 under identical conditions. These results suggest that JAK2 tyrosine kinase is one of the tyrosine kinases involved in signal transduction mediated by IL-11, IL-6, LIF, and OSM.
...
PMID:Identification of a 130-kilodalton tyrosine-phosphorylated protein induced by interleukin-11 as JAK2 tyrosine kinase, which associates with gp130 signal transducer. 817 77

The interaction of prolactin with its receptor in the Nb2 cell line has been shown to induce the phosphorylation of cell-associated proteins and mitogenesis. It has been reported previously that one of these proteins, phosphorylated upon prolactin stimulation, was a tyrosine kinase. We have identified this kinase as JAK2, and demonstrate its association with the prolactin receptor. In addition, we show that the prolactin receptor itself becomes tyrosine phosphorylated upon ligand stimulation in Nb2 cells. These actions are time-dependent and occur rapidly after prolactin stimulation, with first the kinase being activated within 5 min and then the receptor being phosphorylated maximally at 20 min. Moreover, phosphorylation of both JAK2 and the receptor as well as Nb2 cell proliferation are dependent on the concentration of lactogenic hormone, resulting in a bell-shaped response curve similar to that observed in the two site model of hGH action. This indicates that early events in signal transduction as well as later events like mitogenesis and proliferation involve prolactin receptor dimerization. Together these data indicate that the prolactin receptor in Nb2 cells is associated to JAK2 and that upon ligand stimulation, and receptor dimerization, the kinase and the receptor are tyrosine-phosphorylated, which represents the first event in the process of prolactin receptor signal transduction in Nb2 cells.
...
PMID:Prolactin-induced proliferation of Nb2 cells involves tyrosine phosphorylation of the prolactin receptor and its associated tyrosine kinase JAK2. 818 82

To identify tyrosine kinases that may regulate regeneration of the mammalian intestinal epithelium, we amplified portions of the catalytic domains of protein kinases expressed in intestinal crypt cells, using the polymerase chain reaction technique with primers directed against two invariant amino acid sequence motifs found in all kinases. These fragments were cloned and a library of kinase catalytic domains was generated. Sequence analysis of unique clones resulted in the identification of the catalytic domains of several characterized tyrosine kinases, including lyn, hck, c-fgr, tec, JAK2, itk, and the putative receptor kinase ryk, and expression of these kinases has not previously been described in the intestine. We compared the levels of mRNA encoding these kinases in multiple tissues using RNase protection assays, and we localized the expression of hck, lyn, and JAK2 in the intestine using in situ hybridization. In addition, we identified two novel putative catalytic domain sequences. One of these, which we have named sik (src-related intestinal kinase), is expressed at high levels in the gastrointestinal tract and may play a specific role in signal transduction in epithelial tissues.
...
PMID:Tyrosine kinase gene expression in the mouse small intestine. 820 50

We have produced a cell line which lacks the protein tyrosine kinase JAK1 and is completely defective in interferon response. Complementation of this mutant with JAK1 restored the response, establishing the requirement for JAK1 in both the interferon-alpha/beta and -gamma signal transduction pathways. The reciprocal interdependence between JAK1 and Tyk2 activities in the interferon-alpha pathway, and between JAK1 and JAK2 in the interferon-gamma pathway, may reflect a requirement for these kinases in the correct assembly of interferon receptor complexes.
...
PMID:The protein tyrosine kinase JAK1 complements defects in interferon-alpha/beta and -gamma signal transduction. 823 50

Erythropoietin (EPO) regulates the proliferation and differentiation of erythroid cells through interaction with its receptor (EPOR). Although EPOR is a member of the cytokine receptor superfamily and lacks a kinase domain, EPO induces tyrosine phosphorylation, which is correlated with gene transcription and mitogenesis. Here we demonstrate that EPO induces tyrosine phosphorylation of JAK2 kinase and activates its in vitro autophosphorylation. Using EPOR mutants, phosphorylation and activation of kinase activity correlate with the induction of mitogenesis. Furthermore, JAK2 physically associates with a membrane-proximal region of the EPOR cytoplasmic domain that is required for biological activity. The results support the hypothesis that JAK2 is the kinase that couples EPO binding to tyrosine phosphorylation and mitogenesis.
...
PMID:JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin. 834 51

Growth hormone receptor (GHR) forms a complex with a tyrosine kinase, suggesting involvement of a ligand-activated tyrosine kinase in intracellular signaling by growth hormone (GH). Here we identify JAK2, a nonreceptor tyrosine kinase, as a GHR-associated tyrosine kinase. Immunological approaches were used to establish GH-dependent complex formation between JAK2 and GHR, activation of JAK2 tyrosine kinase activity, and tyrosyl phosphorylation of both JAK2 and GHR. The JAK2-GHR and JAK2-erythropoietin receptor interactions described here and in the accompanying paper provide a molecular basis for involvement of tyrosyl phosphorylation in physiological responses to these ligands and suggest a shared signaling mechanism among members of the cytokine/hematopoietin receptor family.
...
PMID:Identification of JAK2 as a growth hormone receptor-associated tyrosine kinase. 834 52


<< Previous 1 2 3 4 5 6 7 8 9 10

---