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K Ueki

Publications and source records attributed to K Ueki.

At least 109 records · Page 6Linked to original sources
PubMed1998

Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas.

BACKGROUND/METHODS: Gliomas are common malignant neoplasms of the central nervous system. Among the major subtypes of gliomas, oligodendrogliomas are distinguished by their remarkable sensitivity to chemotherapy, with approximately two thirds of anaplastic (malignant) oligodendrogliomas responding dramatically to combination treatment with procarbazine, lomustine, and vincristine (termed PCV). Unfortunately, no clinical or pathologic feature of these tumors allows accurate prediction of their response to chemotherapy. Anaplastic oligodendrogliomas also are distinguished by a unique constellation of molecular genetic alterations, including coincident loss of chromosomal arms 1p and 19q in 50%-70% of tumors. We have hypothesized that these or other specific genetic changes might predict the response to chemotherapy and prognosis in patients with anaplastic oligodendrogliomas. Therefore, we have analyzed molecular genetic alterations involving chromosomes 1p, 10q, and 19q and the TP53 (on chromosome 17p) and CDKN2A (on chromosome 9p) genes, in addition to clinicopathologic features in 39 patients with anaplastic oligodendrogliomas for whom chemotherapeutic response and survival could be assessed. RESULTS/CONCLUSIONS: Allelic loss (or loss of heterozygosity) of chromosome 1p is a statistically significant predictor of chemosensitivity, and combined loss involving chromosomes 1p and 19q is statistically significantly associated with both chemosensitivity and longer recurrence-free survival after chemotherapy. Moreover, in both univariate and multivariate analyses, losses involving both chromosomes 1p and 19q were strongly associated with longer overall survival, whereas CDKN2A gene deletions and ring enhancement (i.e., contrast enhancement forming a rim around the tumor) on neuroimaging were associated with a significantly worse prognosis. The inverse relationship between CDKN2A gene deletions and losses of chromosomes 1p and 19q further implies that these differential clinical behaviors reflect two independent genetic subtypes of anaplastic oligodendroglioma. These results suggest that molecular genetic analysis may aid therapeutic decisions and predict outcome in patients with anaplastic oligodendrogliomas.

Adult↗
PubMed1998

Integrin-mediated signal transduction in cells lacking focal adhesion kinase p125FAK.

We have previously shown that integrin-dependent tyrosine phosphorylation of p130Cas (Cas) could be induced in a mouse fibroblast cell line that does not express focal adhesion kinase p125FAK (FAK). By analyzing FAK-deficient (FAK-/-) cells transiently expressing Cas mutant proteins, we demonstrate here that the Src homology 3 (SH3) domain of Cas is indispensable for adhesion-mediated Cas phosphorylation in this mutant cell line. While the FAK directly binds to Cas-SH3, our findings imply that SH3-binding molecule(s) other than FAK might regulate Cas phosphorylation, at least in FAK-/- cells. In this regard, we observed that FAK-/- cells expressed cell adhesion kinase beta (CAKbeta), a protein tyrosine kinase of the FAK subfamily. CAKbeta expressed by FAK-/- cells was associated in vivo with Cas in a Cas-SH3-dependent manner. Moreover, integrin stimulation induces tyrosine phosphorylation of CAKbeta in FAK-/- cells. Thus, our results suggest that CAKbeta contributes to integrin-mediated signal transduction in place of FAK in FAK-deficient cells.

Animals↗
PubMed1998

Growth hormone and prolactin stimulate tyrosine phosphorylation of insulin receptor substrate-1, -2, and -3, their association with p85 phosphatidylinositol 3-kinase (PI3-kinase), and concomitantly PI3-kinase activation via JAK2 kinase.

Growth hormone (GH) and prolactin (PRL) binding to their receptors, which belong to the cytokine receptor superfamily, activate Janus kinase (JAK) 2 tyrosine kinase, thereby leading to their biological actions. We recently showed that GH mainly stimulated tyrosine phosphorylation of epidermal growth factor receptor and its association with Grb2, and concomitantly stimulated mitogen-activated protein kinase activity in liver, a major target tissue. Using specific antibodies, we now show that GH was also able to induce tyrosine phosphorylation of insulin receptor substrate (IRS)-1/IRS-2 in liver. In addition, the major tyrosine-phosphorylated protein in anti-p85 phosphatidylinositol 3-kinase (PI3-kinase) immunoprecipitate from liver of wild-type mice was IRS-1, and IRS-2 in IRS-1 deficient mice, but not epidermal growth factor receptor. These data suggest that tyrosine phosphorylation of IRS-1 may be a major mechanism for GH-induced PI3-kinase activation in physiological target organ of GH, liver. We also show that PRL was able to induce tyrosine phosphorylation of both IRS-1 and IRS-2 in COS cells transiently transfected with PRLR and in CHO-PRLR cells. Moreover, we show that tyrosine phosphorylation of IRS-3 was induced by both GH and PRL in COS cells transiently transfected with IRS-3 and their cognate receptors. By using the JAK2-deficient cell lines or by expressing a dominant negative JAK2 mutant, we show that JAK2 is required for the GH- and PRL-dependent tyrosine phosphorylation of IRS-1, -2, and -3. Finally, a specific PI3-kinase inhibitor, wortmannin, completely blocked the anti-lipolytic effect of GH in 3T3 L1 adipocytes. Taken together, the role of IRS-1, -2, and -3 in GH and PRL signalings appears to be phosphorylated by JAK2, thereby providing docking sites for p85 PI3-kinase and activating PI3-kinase and its downstream biological effects.

Androstadienes↗
PubMed1998

Apoptosis and tumor angiogenesis in cervical cancer after preoperative chemotherapy.

The correlation between apoptosis and tumor angiogenesis in uterine cervical cancer treated by preoperative intraarterial infusion chemotherapy (IAC) was investigated. Cervical cancer samples surgically obtained from 12 patients (stages Ib-IIIb) receiving IAC and from 10 patients (stages Ib-IIb) receiving no chemotherapy and biopsy specimens from the 12 patients before IAC were examined. The apoptotic index (AI) was determined with an in situ end-labeling assay. Intratumoral microvessel density (IMVD) and thymidine phosphorylase (dThdPase) expression were evaluated immunohistochemically using anti-CD34 and anti-dThdPase antibodies. AIs were higher in the 8 patients with complete or partial response to IAC than they were in the 4 nonchemoresponsive patients and in the 10 patients who received no chemotherapy (P < 0.01) and were inversely related to IMVDs (r = 0.724; P < 0.01). AIs and IMVDs after IAC were higher and lower than those before IAC (P < 0.01), respectively. The expression of dThdPase, which has angiogenic activity, was markedly decreased after IAC. These results suggest that the antitumor effects of IAC are closely associated with apoptotic cell death, which may be influenced in part by the extent of tumor angiogenesis inhibition.

Adult↗
PubMed1998

Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats.

Troglitazone (CS-045) is one of the thiazolidinediones that activate the peroxisome proliferator-activated receptor gamma (PPARgamma), which is expressed primarily in adipose tissues. To elucidate the mechanism by which troglitazone relieves insulin resistance in vivo, we studied its effects on the white adipose tissues of an obese animal model (obese Zucker rat). Administration of troglitazone for 15 d normalized mild hyperglycemia and marked hyperinsulinemia in these rats. Plasma triglyceride level was decreased by troglitazone in both obese and lean rats. Troglitazone did not change the total weight of white adipose tissues but increased the number of small adipocytes (< 2,500 micron2) approximately fourfold in both retroperitoneal and subcutaneous adipose tissues of obese rats. It also decreased the number of large adipocytes (> 5,000 micron2) by approximately 50%. In fact, the percentage of apoptotic nuclei was approximately 2.5-fold higher in the troglitazone-treated retroperitoneal white adipose tissue than control. Concomitantly, troglitazone normalized the expression levels of TNF-alpha which were elevated by 2- and 1.4-fold in the retroperitoneal and mesenteric white adipose tissues of the obese rats, respectively. Troglitazone also caused a dramatic decrease in the expression levels of leptin, which were increased by 4-10-fold in the white adipose tissues of obese rats. These results suggest that the primary action of troglitazone may be to increase the number of small adipocytes in white adipose tissues, presumably via PPARgamma. The increased number of small adipocytes and the decreased number of large adipocytes in white adipose tissues of troglitazone-treated obese rats appear to be an important mechanism by which increased expression levels of TNF-alpha and higher levels of plasma lipids are normalized, leading to alleviation of insulin resistance.

Adipocytes↗
PubMed1998

Potential role of protein kinase B in insulin-induced glucose transport, glycogen synthesis, and protein synthesis.

Various biological responses stimulated by insulin have been thought to be regulated by phosphatidylinositol 3-kinase, including glucose transport, glycogen synthesis, and protein synthesis. However, the molecular link between phosphatidylinositol 3-kinase and these biological responses has been poorly understood. Recently, it has been shown that protein kinase B (PKB/c-Akt/Rac) lies immediately downstream from phosphatidylinositol 3-kinase. Here, we show that expression of a constitutively active form of PKB induced glucose uptake, glycogen synthesis, and protein synthesis in L6 myotubes downstream of phosphatidylinositol 3-kinase and independent of Ras and mitogen-activated protein kinase activation. Introduction of constitutively active PKB induced glucose uptake and protein synthesis but not glycogen synthesis in 3T3L-1 adipocytes, which lack expression of glycogen synthase kinase 3 different from L6 myotubes. Furthermore, we show that deactivation of glycogen synthase kinase 3 and activation of rapamycin-sensitive serine/threonine kinase by PKB in L6 myotubes might be involved in the enhancement of glycogen synthesis and protein synthesis, respectively. These results suggest that PKB acts as a key enzyme linking phosphatidylinositol 3-kinase activation to multiple biological functions of insulin through regulation of downstream kinases in skeletal muscle, a major target tissue of insulin.

3T3 Cells↗
PubMed1998

Vascular endothelial growth factor (VEGF) activates Raf-1, mitogen-activated protein (MAP) kinases, and S6 kinase (p90rsk) in cultured rat cardiac myocytes.

Rapid activation of intracellular signaling cascades is induced in cardiac myocytes in response to various external stresses. Vascular endothelial growth factor (VEGF) is a potent angiogenic mitogen secreted from tumor cells and cells exposed to hypoxia such as ischemic myocardial cells. To clarify the mechanisms of how cardiac myocytes respond and adapt to ischemic stresses, we investigated the intracellular signaling cascades in cultured rat cardiac myocytes in response to VEGF. We show that rapid activation of mitogen-activated protein kinase kinase kinase (MAPKKK) of Raf-1, MAP kinases, and S6 kinase (p90rsk) was induced in cardiac myocytes in response to VEGF. This activation of MAP kinases was also induced in fibroblasts. VEGF also caused phosphorylation of the activating transcription factor 2. Furthermore, VEGF strongly induced a transcription factor jun-B mRNA in cardiac myocytes. These results indicated that MAP kinase pathway is rapidly activated in cardiac myocytes and fibroblasts in response to VEGF. It is strongly suggested that cardiac myocytes are one of the targets of VEGF and that cardiac response to ischemic stresses may be at least partly mediated by VEGF.

Activating Transcription Factor 2↗
PubMed1998

Sulfite is released by human neutrophils in response to stimulation with lipopolysaccharide.

Exposure to sulfite, a well-known air pollutant, induces inflammatory reactions characterized by neutrophil infiltration into the airways. Using a simple and sensitive assay for sulfite concentration in biological fluids, we demonstrate herein that human neutrophils released significant amounts of sulfite (1.0 nmol/h/10(7) cells) in response to lipopolysaccharide (LPS), a major component of bacterial endotoxin. A large proportion of the sulfite release by neutrophils was dependent on inorganic sulfate contained in culture media, suggesting production via the sulfate reducing pathway in this response. We also show that glucocorticoids and FK506 completely inhibit LPS-mediated sulfite release by neutrophils. Given the well-known antimicrobial activities of sulfite, our results suggest that sulfite acts as a neutrophil mediator of host defense. A putative role of sulfite as an endogenous biological mediator is further underscored by the observation that in vivo administration of LPS is associated with a marked increase in the serum concentration of sulfite in Wistar rats. Inhibition of sulfite release by immunosuppressive agents may contribute to increased susceptibility to bacterial infection commonly associated with the administration of these drugs.

Animals↗
PubMed1998

New cephalometric images with a workstation. A preliminary report.

OBJECTIVE: This study was designed to test the feasibility of several types of enhancements for cephalometric computed radiographs through use of the Fuji Computed Radiography system (Fuji Photo Film Corp., Tokyo, Japan). STUDY DESIGN: The material consisted of four lateral cephalograms made with the Fuji Computed Radiography system that were enhanced by varying the gradient levels before processing by means of both A-type (straight gradation) curves and workstation-type (peaked) curves. The four workstation-type images were set with optical densities at the peak of the curve at 1.5, 1.7, 1.9, and 2.1. Ten observers evaluated eight anatomic landmarks comparing pairs of workstation-type images. The best workstation-type image was then compared with the A-type image for the same landmarks. RESULTS: For the four workstation-type images the best visualization of the anatomic landmarks was seen with workstation-type image 3, which had a maximum optical density of 1.9. Image 3 was also superior to the results of A-type image processing for most of the landmarks. CONCLUSION: Image enhancement with the application of a computed radiography system is effective for study of lateral cephalograms.

Cephalometry↗
PubMed1998

Molecular genetic correlates of p16, cdk4, and pRb immunohistochemistry in glioblastomas.

The vast majority of glioblastomas have CDKN2A, CDK4, or RB gene alterations that perturb the p16-cdk4-pRb cell cycle regulatory cascade. To explore whether immunohistochemical methods provide an alternative means of assessing this pathway, we studied 25 glioblastomas using a combination of molecular genetic and immunohistochemical assays. Homozygous deletion of the CDKN2A gene was detected in 12 of 25 (48%) cases, CDK4 amplification in 4 of 25 (16%) tumors, and loss of heterozygosity at the RB gene in 8 of 22 (36%) informative cases. Five of 25 (20%) glioblastomas had diffuse p16 immunohistochemical positivity. Significantly, all of these had either CDK4 amplification or RB LOH, suggesting that p16 immunopositivity only occurs in those tumors with alterations of another component in the pathway. Nineteen (76%) cases were uniformly immunonegative for p16, and 12 (48%) had CDKN2A homozygous deletions, but the remaining 7 cases lacked CDKN2A deletions, mutations and promoter methylation. All glioblastomas stained diffusely for cdk4, irrespective of CDK4 gene amplification status. Extensive pRb staining was present in most cases that maintained both RB alleles, and absent in most cases with RB loss, but there were notable discrepancies. Thus, p16 and pRb immunohistochemistry cannot replace molecular genetic analysis of this critical regulatory cascade; instead, the combined results hint at complex regulation of this cell cycle checkpoint. From a practical point of view, although p16 immunonegativity does not necessarily indicate CDKN2A deletion, diffuse positive p16 immunostaining strongly suggests either CDK4 amplification or RB loss and excludes CDKN2A deletion.

Brain↗
PubMed1998

Effects of sex steroids and growth factors on invasive activity and 5'-deoxy-5-fluorouridine sensitivity in ovarian adenocarcinoma OMC-3 cells.

Effects of sex steroids (estradiol-17 beta, E2; progesterone, Prog) and growth factors (epidermal growth factor, EGF; transforming growth factor-alpha, TGF-alpha) on invasive activity and 5'-deoxy-5-fluorouridine (5'-dFUrd) sensitivity of ovarian adenocarcinoma OMC-3 cells were investigated. Tumor cell migration along a gradient of substratum-bound fibronectin and invasion into reconstituted basement membrane were inhibited by 10 microM Prog, but stimulated by 0.1-10 nM EGF and TGF-alpha in a concentration-dependent manner. E2 did not have any effect on tumor cell migration or invasion. The zymography of tumor conditioned medium showed that the treatment of OMC-3 cells with EGF and TGF-alpha resulted in increases of type IV collagenase, stromelysin and urokinase-type plasminogen activator (uPA). EGF and TGF-alpha up-regulated thymidine phosphorylase (dThdPase) expression of tumor cells and consequently enhanced the antiproliferative action of 5'-dFUrd, which is converted to 5-fluorouracil by dThdPase. E2 and Prog did not have significant effects on the expression of proteolytic enzymes and dThdPase, or on the 5'-dFUrd sensitivity of tumor cells. The inhibitory effect of Prog on tumor cell invasion may depend on its inhibitory action on the motility of tumor cells. These results suggest that EGF and TGF-alpha simultaneously up-regulate the potential of ovarian adenocarcinoma cells to invade extracellular matrices and their dThdPase expression, both of which are associated with the specific action of 5'-dFUrd selectively to kill tumor cells with high invasive and metastatic potential.

Basement Membrane↗
PubMed1998

Risk of recurrent subarachnoid hemorrhage after complete obliteration of cerebral aneurysms.

BACKGROUND AND PURPOSE: The neck clipping of cerebral aneurysms is a well-established treatment for subarachnoid hemorrhage (SAH) caused by aneurysmal rupture. However, it is still unclear how great a risk of recurrence patients with a successfully treated aneurysm carry over a long-term period. METHODS: Of 425 patients with SAH surgically treated in Aizu Chuou Hospital from 1976 to 1994, 220 cases meeting the following criteria were studied: (1) all aneurysms detected by 3- or 4-vessel cerebral angiography were clipped, (2) complete obliteration of aneurysm(s) was confirmed by postoperative angiography, and (3) the patient survived >3 years. All patients were traced until January 1998 for recurrent SAH or death. The mean follow-up period was 9.9 (range, 3 to 21) years. RESULTS: Six patients (2.7%) had recurrent SAH, each with an interval ranging from 3 to 17 years (mean, 11 years) since the original treatment. In addition, 2 patients were found to have regrowth of the originally operated aneurysms. The cumulative recurrence rate of SAH, calculated using the Kaplan-Meier method, was 2.2% at 10 years and 9. 0% at 20 years after the original treatment. CONCLUSIONS: The recurrence rate was considerably higher than the previously reported risk of SAH in the normal population, and the rate increased with time. These data indicate that patients with ruptured cerebral aneurysms still carry higher risks for SAH in a long-term period, even after complete obliteration of the aneurysm, and that periodic examination to detect recurrent aneurysms may be indicated for such patients.

Adult↗
PubMed1998

Growth hormone-induced tyrosine phosphorylation of EGF receptor as an essential element leading to MAP kinase activation and gene expression.

GH binding to its receptor, which belongs to the cytokine receptor superfamily, activates Janus kinase (JAK) 2 tyrosine kinase, thereby activating a number of intracellular key proteins such as STAT (signal transducers and activators of transcription) proteins and mitogen-activated protein (MAP) kinases, which finally lead to GH's biological actions including gene expression. In contrast to receptor tyrosine kinases, the signalling pathways leading to MAP kinase activation by GH are poorly understood but appear to involve Grb2 and Shc. We now show that GH stimulated tyrosine phosphorylation of epidermal growth factor receptor (EGFR) and its association with Grb2, and concomitantly stimulated MAP kinase activity in liver, a major target tissue. Expression of EGFR and its mutants into CHO-GH receptor (GHR) cells revealed that GH-induced full activation of MAP kinase and c-fos expression required tyrosine phosphorylation sites of EGFR but not its intrinsic tyrosine kinase activity. Moreover, by also using dominant negative JAK2 and in vitro kinase assay, we demonstrated that tyrosine 1068 of EGFR was evidently one of the major phosphorylation and Grb2 binding sites stimulated by GH via JAK2. These data suggest that the role of EGFR in GH signalling is to be phosphorylated by JAK2, thereby providing docking sites for Grb2 and activating MAP kinases and gene expression. This novel cross talk pathway may provide the first example of the hormone and cytokine receptor superfamily transducing signals via associated nonreceptor tyrosine kinase by phosphorylating growth factor receptor and utilizing it as a docking protein independent of its receptor tyrosine kinase activity.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Pentavalent technetium-99m-dimercaptosuccinic acid scintigraphy in renal osteodystrophy.

Pentavalent 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy and 99mTc-hydroxymethylene diphosphonate (HMDP) bone scan were performed in one patient with renal osteodystrophy (ROD) before and after vitamin D3 pulse therapy. The bone scan showed diffusely increased tracer uptake in the whole skeleton, and no change of tracer distribution was noted before or after vitamin D3 pulse therapy. However, 99mTc(V)-DMSA scintigraphy revealed diffusely increased tracer uptake in the whole skeleton before therapy, and markedly decreased tracer uptake in the bones was seen at 5 mo after therapy. Increased uptake of 99mTc(V)-DMSA was observed at 7 mo after therapy, which reflected the laboratory findings. Technetium-99m-(V)-DMSA scintigraphy appeared to be more sensitive than the conventional 99mTc-HMDP bone scan in assessing the characteristics and therapeutic effect of bone disease in ROD.

Adult↗
PubMed1998

Tumor recurrence in patients with early gastric cancer: a clinicopathologic evaluation.

We conducted a retrospective study on 711 patients with early gastric cancer. Twenty-two patients (4.0%) developed recurrent disease and 21 died of recurrence during this study. One hundred and sixty-three patients died of unrelated or unknown causes. The recurrence patterns of 22 patients were as follows: hematogeneous metastasis to the liver in 11 patients, peritoneal dissemination in 3, recurrence in the remnant stomach in 3, and in the distant lymphonodes in 1. The mean survival period of patients with recurrent disease was 50.4 months, and 7 of these patients (31.8%) died more than 5 years after surgery. A retrospective clinicopathologic evaluation of the 22 patients and 526 patients without recurrence revealed significant differences between the two groups with respect to mean age at the time of surgery (62.5 years in the recurrent group vs 57.3 years in the nonrecurrent group), tumor size (41.2 vs 30.6 mm), depth of invasion (submucosal cancer: 19 vs 256), lymphnode metastasis (11 vs 48), lymphatic (11 vs 89) and venous (7 vs 18) invasion, and operative curability (curability B: 8 vs 48). Three patients with intramucosal cancer who died of hematogenous and/or peritoneal recurrence within 7 years after surgery had neither lymphnode metastasis nor lymphatic or venous invasion, suggesting that new techniques are needed for prediction of recurrent disease in patient with early gastric cancer.

Adult↗
PubMed1997

Cloning and tyrosine phosphorylation of a novel invertebrate immunocyte protein containing immunoreceptor tyrosine-based activation motifs.

Immunoreceptor tyrosine-based activation motif (ITAM) plays an important role in signal transduction through mammalian T-cell and B-cell antigen receptors and Fc receptors. The ITAM has been found only in vertebrate immunocytes. Ascidians are intriguing invertebrates from the viewpoint of the evolution of immune systems because they are considered to be ancestors of the vertebrates. We have previously shown that the monoclonal antibody A74 inhibits cellular defense reactions of the ascidian. In the present studies, we found that the A74 antigen protein has two ITAMs and several motifs that are proposed to function in signal transduction. The A74 protein is tyrosine-phosphorylated and associated with other proteins in the initial stages of cellular defense reactions. The ITAMs of the A74 protein are tyrosine-phosphorylated by a c-Src kinase in vitro. The A74 protein provides a key to the understanding of the origin of vertebrate immune systems.

Amino Acid Sequence↗
PubMed1997

Tyrosine phosphorylation of the EGF receptor by the kinase Jak2 is induced by growth hormone.

When growth hormone binds to its receptor, which belongs to the cytokine receptor superfamily, it activates the Janus kinase Jak2 which has tyrosine-kinase activity and initiates an activation of several key intracellular proteins (for example, mitogen-activated protein (MAP) kinases) that eventually execute the biological actions induced by growth hormone, including the expression of particular genes. In contrast to receptors that themselves have tyrosine kinase activity, the signalling pathways leading to MAP kinase activation that are triggered by growth hormone are poorly understood, but appear to be mediated by the proteins Grb2 and Shc. We now show that growth hormone stimulates tyrosine phosphorylation of the receptor for epidermal growth factor (EGFR) and its association with Grb2 and at the same time stimulates MAP kinase activity in liver, an important target tissue of growth hormone. Expression of EGFR and its mutants revealed that growth-hormone-induced activation of MAP kinase and expression of the transcription factor c-fos requires phosphorylation of tyrosines on EGFR, but not its own intrinsic tyrosine-kinase activity. Moreover, tyrosine at residue 1,068 of the EGFR is proposed to be one of the principal phosphorylation sites and Grb2-binding sites stimulated by growth hormone via Jak2. Our results indicate that the role of EGFR in signalling by growth hormone is to be phosphorylated by Jak2, thereby providing docking sites for Grb2 and activating MAP kinases and gene expression, independently of the intrinsic tyrosine kinase activity of EGFR. This may represent a novel cross-talk pathway between the cytokine receptor superfamily and growth factor receptor.

Adaptor Proteins, Signal Transducing↗