Search PubMed⌕ Search

Biomedical subjects

T Takada

Publications and source records attributed to T Takada.

At least 73 records · Page 4Linked to original sources
PubMed2000

[A case of isolated sarcoidosis of the cerebral falx].

A 28 year-old man complaining of intermittent headaches for a month following an episode of general convulsions was admitted to the Department of Neurosurgery of our hospital. His brain CT scan showed a well-enhanced mass growing symmetrically along the anterior cerebral falx in a manner compatible with meningioma. Nothing abnormal was detected in chest radiography on admission. Histopathological examination of the mass after partial resection revealed multiple epithelioid cell granulomas with giant cells indicating sarcoidosis. After 4 weeks of treatment with oral prednisolone 30 mg/day, bronchoalveolar lavage was performed in our department. In the lavage fluid, both the total cell count and the percentage of lymphocytes were elevated. The lung specimens obtained by transbronchial biopsy also showed epithelioid cell granulomas. CNS sarcoidosis is reportedly usually observed in the vicinity of the hypothalamus with other organ involvement. In the present case, differential diagnosis of sarcoidosis from meningioma was difficult because the solitary lesion was growing along the anterior cerebral falx without radiographic evidence of bilateral hilar lymphadenopathy.

Adult↗
PubMed1999

Regulation of phosphorylation level and distribution of PTP36, a putative protein tyrosine phosphatase, by cell-substrate adhesion.

Recently we have cloned a putative protein tyrosine phosphatase, PTP36/PTPD2/pez, which possesses a domain homologous to the N-terminal half of band 4.1 protein. In mouse fibroblasts adhered to substrates, PTP36 was phosphorylated on serine residues. PTP36 was found to make complexes with serine/threonine kinase(s), which phosphorylated PTP36 in vitro. PTP36 was dephosphorylated rapidly when the cell-substrate adhesion was disrupted and it was phosphorylated again along with the reattachment of the cells to fibronectin. Rephosphorylation of PTP36 seemed to depend on actin polymerization since it was inhibited by cytochalasin D. The cell detachment also induced the translocation of PTP36 into the membrane-associated cytoskeletal fraction. Staurosporine and ML-9, which inhibited the phosphorylation of PTP36 in vivo, induced the translocation of PTP36 too. On the contrary, when the dephosphorylation of PTP36 was inhibited by okadaic acid, no translocation of PTP36 was induced by the cell detachment. These results demonstrate that the cell-substrate adhesion and cell spreading regulates the intracellular localization of PTP36 most likely through its phosphorylation and therefore, PTP36 may play important roles in the signal transduction pathway of cell-adhesion.

Animals↗
PubMed1999

Posterior occipitocervical reconstruction using cervical pedicle screws and plate-rod systems.

STUDY DESIGN: This retrospective study was conducted to analyze the clinical results in 26 patients with lesions at the craniocervical junction that had been treated by occipitocervical reconstruction using pedicle screws in the cervical spine and occipitocervical rod systems. OBJECTIVES: To evaluate the effectiveness of pedicle screw fixation in occipitocervical reconstructive surgery and to introduce surgical techniques. SUMMARY OF BACKGROUND DATA: Many methods of occipitocervical reconstruction have been reported, but there have been no reports of occipitocervical reconstruction using pedicle screws and occipitocervical rod systems for reduction and fixation. METHODS: Twenty-six patients with lesions at the craniocervical junction underwent reconstructive surgery using pedicle screws in the cervical spine and occipitocervical rod systems. The occipitocervical lesions were atlantoaxial subluxation associated with basilar invagination, which was caused by rheumatoid arthritis in 19 patients and other disorders in 7. The lowest cervical vertebra of fusion in 16 patients was C2, and the remaining 10 patients underwent fusion downward from C3 to C7. Flexion deformity of the occipitoatlantoaxial complex was corrected by application of extensional force, and upward migration of the odontoid process was reduced by application of combined force of extension and distraction between the occiput and the cervical pedicle screws. RESULTS: Solid fusion was achieved in all patients except two with metastatic vertebral tumors who did not receive bone graft for fusion. Correction of malalignment at the craniocervical junction was adequate, and postoperative magnetic resonance imaging showed improvement of anterior compression of the medulla oblongata. There were no neurovascular complications of cervical pedicle screws. CONCLUSIONS: Occipitocervical reconstruction by the combination of cervical pedicle screws and occipitocervical rod systems provided the high fusion rate and sufficient correction of malalignment in the occipitoatlantoaxial region. Results of this study showed the effectiveness of cervical pedicle screw as a fixation anchor for occipitocervical reconstruction.

Adult↗
PubMed1999

Effects of overexpression of PTP36, a putative protein tyrosine phosphatase, on cell adhesion, cell growth, and cytoskeletons in HeLa cells.

Non-receptor-type putative protein tyrosine phosphatase-36 (PTP36), also known as PTPD2/Pez, possesses a domain homologous to the N-terminal half of band 4.1 protein. To gain insight into the biological function of PTP36, we established a HeLa cell line, HtTA/P36-9, in which the overexpression of PTP36 was inducible. PTP36 expressed in HeLa cells was enriched in the cytoskeleton near the plasma membrane. There was little endogenous PTP36 detectable in uninduced HtTA/P36-9 cells or in the parental HeLa cells. Upon induction of PTP36 overexpression, HtTA/P36-9 cells spread less well, grew more slowly, and adhered to the extracellular matrix proteins less well than uninduced cells. Moreover, decreases in the actin stress fibers and the number of focal adhesions were observed. The tyrosine phosphorylation of the focal adhesion kinase induced by lysophosphatidic acid was suppressed in the HtTA/P36-9 cells overexpressing PTP36. These results indicate that PTP36 affects cytoskeletons, cell adhesion, and cell growth, thus suggesting that PTP36 is involved in their regulatory processes.

Cell Adhesion↗
PubMed1999

PI 3-kinase gamma and protein kinase C-zeta mediate RAS-independent activation of MAP kinase by a Gi protein-coupled receptor.

Receptors coupled to the inhibitory G protein Gi, such as that for lysophosphatidic acid (LPA), have been shown to activate MAP kinase through a RAS-dependent pathway. However, LPA (but not insulin) has now been shown to activate MAP kinase in a RAS-independent manner in CHO cells that overexpress a dominant-negative mutant of the guanine nucleotide exchange protein SOS (CHO-DeltaSOS cells). LPA also induced the activation of MAP kinase kinase (MEK), but not that of RAF1, in CHO-DeltaSOS cells. The RAS-independent activation of MAP kinase by LPA was blocked by inhibitors of phosphatidylinositol 3-kinase (PI3K) or by overexpression of a dominant-negative mutant of the gamma isoform of PI3K. Furthermore, LPA induced the activation of the atypical zeta isoform of protein kinase C (PKC-zeta) in CHO-DeltaSOS cells in a manner that was sensitive to wortmannin or to the dominant-negative mutant of PI3Kgamma, and overexpression of a dominant-negative mutant of PKC-zeta inhibited LPA-induced activation of MAP kinase. These observations indicate that Gi protein-coupled receptors induce activation of MEK and MAP kinase through a RAS-independent pathway that involves PI3Kgamma-dependent activation of atypical PKC-zeta.

Animals↗
PubMed1999

Three-dimensional reconstruction of the ventral and dorsal pancreas: a new insight into anatomy and embryonic development.

The recent introduction of limited resections of the ventral pancreas for benign disease and for low-grade malignancies calls for a thorough understanding of its anatomy. The two embryonic anlagen were characterized and distinguished through a comprehensive study of their macroscopic, histologic, and immunohistochemical characteristics in 20 autopsy specimens before reconstruction. Sections were histologically stained with hematoxylin-eosin and Grimelius and immunohistochemically stained with antibodies to insulin, glucagon, somatostatin, and pancreatic polypeptide by the avidin biotin complex method. The ventral and dorsal anlagen of the pancreas were reconstructed from eight autopsy specimens, using the "macroserial" method, after serial sectioning and immunohistochemical staining with anti-pancreatic polypeptide antibodies. Compared with the dorsal pancreas, the ventral pancreas was characterized by the presence of smaller and more closely packed lobuli, irregular rather than uniform islets of Langerhans, and rich immunostaining with anti-pancreatic polypeptide. Construction of the two anlagen showed that the dorsal pancreas consisted of the anterior part of the head of the pancreas, and the body and tail of the pancreas, while the ventral pancreas consisted of the posterior part of the head of the gland and the upper two-thirds (62.5%) or all (37.5%) of the uncinate process. The ventral pancreas was related to the right lateral surface of the superior mesenteric vein extending to the back. However, it did not extend across the front surface of the superior mesenteric vein to the left as previously described. The uncinate process was also located posterior to but not anterior to the superior mesenteric vein. The contributions of the ventral and dorsal anlagen to the anatomy of the pancreas gland as demonstrated in this study differ, in some relevant features, from the classical descriptions in the medical literature. The current anatomical findings add essential knowledge for the pancreatic surgeon who contemplates tissue-preserving resections.

Adolescent↗
PubMed1999

Early and late complications of pylorus-preserving pancreatoduodenectomy in Japan 1998.

Early (within 1 month after operation) and late (more than 1 month after surgery) complications after pylorus-preserving pancreatoduodenectomy (PpPD) were analyzed in 1066 Japanese patients collected from 74 authentic institutions in Japan. As early postoperative complications after PpPD, delayed gastric emptying was evident in 46% of patients, pancreatoenterostomy leakage in 16%, intra-abdominal infection in 14%, cholangitis in 8.9%, hepaticojejunostomy leakage in 4.7%, intra-abdominal hemorrhage in 3. 5%, upper gastrointestinal hemorrhage in 3.2%, and duodenojejunostomy leakage in 2.0%. Delayed gastric emptying resolved 1-24 months after PpPD (mean, 3.1 months). The direct operative mortality (death within 1 month after the operation) was 2. 4%. Univariate and multivariate analysis of pancreatoenterostomy leakage showed that male sex (P = 0.0151) and soft consistency of the pancreas (P < 0.0001) were independent significant factors. Univariate analysis of delayed gastric emptying showed that establishment of gastrostomy (P < 0.0001), length of the preserved duodenum (P = 0.0406), gastric juice output (P = 0.0001), length of gastric tube placement (P < 0.0001), and administration of cisapride (P = 0.0059) were significant variants. As late complications, stomal ulcer was evident in 3.6% of patients, cholangitis in 6.7%, and liver abscess in 1.2%. Glucose intolerance appeared in 61 patients, resolved in 15, showed no change in 170, was absent in 695, and was ameliorated in 17. As a result, the dosage of hypoglycemic agents or insulin showed no change in 187 patients, decreased in 16, and increased in 52. Diabetes appeared 0-42 months after PpPD (mean, 102 months). When present, diabetes deteriorated 0-36 months postoperatively (mean, 6.3 months). Univariate analysis of the appearance or deterioration of diabetes showed that diabetes occurred more frequently in the following patients; those with Billroth I reconstruction compared with those with Billroth II (P = 0.0041), those with pancreatogastrostomy vs those with pancreatojejunostomy (P = 0.0229), those with pancreatogastrostomy vs those with end-to-side pancreatojejunostomy (P = 0.0165), and those with total tube drainage vs those with pancreatico-whole thickness anastomosis (P = 0.0392); a high American Society of Anesthesiologist (ASA) score (P = 0.0211) and pancreatoenterostomy leakage (P = 0.0361) were also significant factors. Postoperative body weight loss (>3 kg) was evident in 62% of patients. Body weight loss reached a maximum 4.2 +/- 5.8 months after PpPD (mean, 6.0 kg) and returned to the preoperative level 4.8 months thereafter. These results suggest that PpPD has been performed safely in Japan, the operative mortality being 2.4%. However, delayed gastric emptying was evident in 46% of the patients and pancreatoenterostomy leakage in 16%. Impairment of glucose tolerance occurred in about 10% of patients more than 1 month after PpPD. Therefore, during the early postoperative period, patients should be closely monitored for pancreatoenterostomy leakage and delayed gastric emptying and in the late postoperative period, glucose tolerance should be carefully followed-up.

Adolescent↗
PubMed1999

Alteration of muscle fiber composition linking to insulin resistance and hypertension in fructose-fed rats.

The aim of this study was to examine the role of muscle fiber composition in insulin resistance and the effect of a calcium channel antagonist on insulin sensitivity in fructose-induced insulin resistant and hypertensive rats. Six-week-old male Sprague-Dawley rats were fed either normal rat chow (control) or fructose-rich diet (FFR). For the last 2 weeks of a 6-week period of either diet, the rats were treated, by gavage, with gum arabic solution (control or FFR) or a dihydropyridine calcium channel antagonist, benidipine hydrochloride (3 mg/kg/day: FFR + Ca), then the euglycemic hyperinsulinemic glucose clamp technique was performed to evaluate insulin sensitivity. Blood pressure was measured weekly for 6 weeks. At the end of the glucose clamp, the soleus muscle was dissected out for determination of muscle fiber composition by ATPase methods. Blood pressure was elevated at 2 weeks after the start of fructose-rich chow feeding and persisted thereafter throughout the study. Blood pressure at the glucose clamp in the FFR was significantly higher than that in the control group (142 +/- 2 v 155 +/- 2 mm Hg, P < .01) and the calcium antagonist significantly lowered blood pressure of FFR (136 +/- 6 mm Hg for FFR +/- Ca, P < .05). The average rate of glucose infusion during glucose clamp, as a measure of insulin sensitivity (M value), was significantly lower in the FFR than in the control (15.4 +/- 0.4 v 10.9 +/- 0.6 mg/kg/min, P < .01). The calcium channel antagonist partially improved the M value compared to that of FFR (13.4 +/- 0.7 mg/kg/min in FFR +/- Ca, P < .01 compared to FFR, P < .05 compared to control). The composite ratio of type I fiber in soleus muscle was significantly decreased in FFR compared to control (81.7 +/- 1.5% v 75.0 +/- 1.7%, P < .01), and the composite ratio of type I fiber in rats treated with the calcium channel antagonist (FFR +/- Ca) recovered to the control level (79.9 +/- 1.1%, P < .05 compared to FFR). The M value was significantly correlated with the compositions of type I and type II fibers (for type I fibers, r = 0.80, P < .01; for type II fibers, r = -0.81, P < .01). These results suggest that fiber composition of skeletal muscle links insulin resistance and that a calcium channel antagonist may modulate muscle fiber composition in hypertensive animal model, fructose-fed rats.

Animals↗
PubMed1999

Effects of digoxin-specific antibody Fab fragment (Digibind) on blood pressure and renal water-sodium metabolism in 5/6 reduced renal mass hypertensive rats.

The importance of increased endogenous digitalis-like factor (EDLF) in volume-expanded hypertension has been generally agreed. To further clarify the role of EDLF on the development of hypertension and renal water-sodium handling in 5/6 reduced renal mass hypertensive rats (RRM), we studied the effects of acute administration of digoxin-specific antibody Fab fragment (Digibind) in the early phase and the chronic phase of hypertension in RRM. RRM and sham-operated rats were given 1% saline for 1 or 4 weeks. RRM were injected Digibind (60 mg/kg) or vehicle (0.9% saline) intravenously in the first or fourth week under thiobutabarbital anesthesia. All sham-operated rats were administered Digibind under the same condition. Digibind altered neither blood pressure, heart rate, urine volume, nor urinary sodium excretion in sham-operated rats. However, Digibind produced a gradual but significant decline in mean arterial pressure to the level slightly above that in sham-operated rats from 153 +/- 5 to 131 +/- 5 mm Hg in the first week and from 181 +/- 6 to 129 +/- 4 mm Hg in the fourth week without any significant change in heart rate. The decrease in mean arterial pressure at 160 min after Digibind administration in the fourth week (-48 +/- 5 mm Hg) was greater than that in the first week (-22 +/- 4 mm Hg). No differences were observed in urine volume, urinary sodium excretion, or plasma norepinephrine concentration between Digibind and vehicle-treated RRM in either week. These data suggest that EDLF would contribute to both the early and chronic phase in the development of hypertension in RRM.

Animals↗
PubMed1999

Effects of immunization with tumor cells double transfected with interleukin-2 (IL-2) and interleukin-12 (IL-12) genes on artificial metastasis of colon26 cells in BALB/c mice.

In order to induce tumor specific cytotoxicity, the poorly immunogenic murine colon cancer cell colon26 was transfected with murine IL-2 cDNA and/or IL-12 cDNA and their anti-tumor effects were investigated. Double transfectants produced murine IL-2 and murine IL-12, the same as single transfectants. Intraperitoneal administration of double transfectants inhibited pulmonary metastasis of colon26 inoculated intravenously to a stronger degree than that of single transfectants. Splenocytes from mice administered double transfectants intraperitonealy showed higher cytolytic activity against colon26 than those from mice administered single transfectants, and also showed cytolytic activity against murine B16-BL6 melanoma. In the NK cell-depleted mice, double transfectants inhibited pulmonary metastasis from the control markedly, but could not do completely, the same as in the NK cell-reserved mice. The difference of the metastatic colonies between NK cell-depleted mice and the control was much greater than that between NK cell-depleted mice and NK cell-reserved mice. These results suggested that cytotoxic T lymphocytes might participate in this anti-tumor effect.

Animals↗
PubMed1999

Flowcytometric analysis of bronchoalveolar lavage fluid cells in polymyositis/dermatomyositis with interstitial pneumonia.

OBJECTIVE: Interstitial lung disease (ILD) is a complication occurring in 10-30% of patients with polymyositis/dermatomyositis (PM/DM) as well as in those with progressive systemic sclerosis (PSS). Clinical features are different between these two disease states, notably with respect to the duration of manifestations, pathological findings, response to steroid therapy etc. However, dissimilarities in pulmonary inflammatory cell characteristics, which, if present at all, would be of critical importance, remain as yet to be clarified. METHODOLOGY: The phenotypes of lymphocytes and alveolar macrophages in bronchoalveolar lavage fluid (BALF) were analysed to elucidate phenotypic peculiarity of pulmonary inflammatory cells of ILD in PM/DM. Eight PM/DM patients with ILD (mean age 47.9 years) were examined by bronchofibrescopy under local anaesthesia. Bronchoalveolar lavage was performed from the right middle lobe using four 50 mL aliquots of normal saline and the recovered fluid was compared with BALF of ILD in PSS. RESULTS: Bronchoalveolar lavage fluid cells of PM/DM patients with ILD showed an increased percentage of CD8+ lymphocytes, in particular CD8+ histocompatibility leucocyte antigen-DR positive lymphocytes and CD8+ CD11b-lymphocytes, both of which represent cytotoxic T cells. However, phenotypic differences in these lymphocytes were not found between PM and DM. The percentage of alveolar macrophages with expression of histocompatibility leucocyte antigen-DQ was significantly different among the three groups (PM/DM, PSS, healthy volunteers). CONCLUSIONS: Cytotoxic T cells may be major pulmonary inflammatory cells of ILD in PM/DM with no apparent difference between PM and DM. In contrast, ILD in PSS was suggested as being likely to be characterized by activated macrophage.

Adult↗
PubMed1999

The lumbar artery perforator based island flap: anatomical study and case reports.

A lumbar artery island flap can be elevated based on a single lumbar artery. We studied the vascular anatomy using 21 specimens of lumbar arteries in 11 cadavers, and investigated the skin territory of the artery using fluorescein injection. We observed lumbar perforators emerging through the lumbar fascia at the lateral border of the erector spinae muscle, situated 5-9 cm from the midline. The diameter of the vascular bundle at the site of perforation ranged from 1 to 5 mm. Perforators of the second and fourth lumbar arteries were much more developed than others. The cutaneous territory supplied by the second lumbar artery extended from the posterior midline to the lateral border of the rectus sheath, and at least 10 cm above the anterosuperior iliac spine. We transferred four clinical flaps for coverage of ulcers on the lower back. All flaps survived and their donor site defects were closed primarily. The cadaver dissection, the injection study and our clinical success have confirmed the feasibility of lumbar artery island flaps.

Humans↗
PubMed1999

Characteristics of two forms of alpha-amylases and structural implication.

Complete (Ba-L) and truncated (Ba-S) forms of alpha-amylases from Bacillus subtilis X-23 were purified, and the amino- and carboxyl-terminal amino acid sequences of Ba-L and Ba-S were determined. The amino acid sequence deduced from the nucleotide sequence of the alpha-amylase gene indicated that Ba-S was produced from Ba-L by truncation of the 186 amino acid residues at the carboxyl-terminal region. The results of genomic Southern analysis and Western analysis suggested that the two enzymes originated from the same alpha-amylase gene and that truncation of Ba-L to Ba-S occurred during the cultivation of B. subtilis X-23 cells. Although the primary structure of Ba-S was approximately 28% shorter than that of Ba-L, the two enzyme forms had the same enzymatic characteristics (molar catalytic activity, amylolytic pattern, transglycosylation ability, effect of pH on stability and activity, optimum temperature, and raw starch-binding ability), except that the thermal stability of Ba-S was higher than that of Ba-L. An analysis of the secondary structure as well as the predicted three-dimensional structure of Ba-S showed that Ba-S retained all of the necessary domains (domains A, B, and C) which were most likely to be required for functionality as alpha-amylase.

Amino Acid Sequence↗
PubMed1999

Surgery for carcinoma of the pancreas in Japan. Past, present, and future aspects.

Pancreatic cancer surgery was first performed in Japan in the 1940s, although it was not until the 1970s that pancreatic resectional surgery became widely available. In the late 1970s, influenced by the application of regional pancreatectomy by Fortner and colleagues, several institutions in Japan introduced radical pancreatic cancer surgery. Aggressive strategies in pancreatic cancer surgery were approved in Japan in the 1980s. Japanese surgeons introduced additional modifications to pancreatic cancer surgery, including radical pancreatoduodenectomy with extended lymph node and connective tissue dissection and portal vein resection. However, it became clear that such extended operations impair the quality of life of the patient, even though the resectability of cancer increased to up to about 50%. Improvements to radical pancreatoduodenectomy were therefore introduced. Pylorus-preserving pancreatoduodenectomy with extended lymphadenectomy, connective tissue dissection, and portal vein resection is a Japanese modification to radical pancreatectomy that improves the quality of life of the patient and does not reduce the survival rate. Another modification applicable to low-grade malignancies is organ-preserving pancreatectomy, such as duodenum-preserving total pancreatic head resection, ventral pancreatectomy, and medial or segmental pancreatectomy. Although aggressive Japanese surgical strategies have provided important data, most studies have been retrospective. In the near future, Japanese surgeons will need to reevaluate their strategies in term of the importance of extended lymphadenectomy with connective tissue dissection and its influence on long-term survival of patients. Such reevaluation will require randomized controlled trials performed according to a detailed and strict protocol.

Duodenum↗
PubMed1999

[The salvage chemotherapy for refractory testicular cancer with novel anticancer agents].

Despite the generally high cure rate in patients with metastatic testicular cancer, 20% to 30% of treated patients will become candidates for salvage chemotherapy. We reviewed the recent salvage chemotherapy trials of refractory diseases. CPT-11 is a new derivative of camptothecin and has activity in a variety of solid tumors. We evaluated the antitumor effect of combination chemotherapy using CDDP and CPT-11 against refractory testicular cancer. Fourteen patients who failed to achieve complete remission with salvage chemotherapy were treated with combination chemotherapy with CPT-11 and CDDP or 254-S (nedaplatin) as third line chemotherapy. Six patients remain alive and disease-free and 5 patients died of disease. The combination of CPT-11 and either CDDP or nedaplatin was significantly more effective than other salvage therapy regimens such as VIP. Paclitaxel, ifosfamide, etoposide regimens were also effective in patients with refractory testicular tumors. We concluded that these combination regimens demonstrated significant activity against refractory testicular tumor and further investigation is warranted.

Adult↗
PubMed1998

Lysophosphatidic acid-induced association of SHP-2 with SHPS-1: roles of RHO, FAK, and a SRC family kinase.

SHPS-1 is an approximately 120 kDa glycosylated receptor like protein that contains three immunoglobulin-like domains in its extracellular region as well as four potential tyrosine phosphorylation and SRC homology 2 (SH2) domain binding sites in its cytoplasmic region. Lysophosphatidic acid (LPA) stimulated the rapid tyrosine phosphorylation of SHPS-1 and its subsequent association with SHP-2, a protein tyrosine phosphatase containing SH2 domains in Rat-1 fibroblasts. LAP-induced tyrosine phosphorylation of SHPS-1 was inhibited by Clostridium botulinum C3 exoenzyme (which inactivates RHO) but not by pertussis toxin. The protein kinase C activator phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA) also stimulated tyrosine phosphorylation of SHPS-1; however, down-regulation of protein kinase C by prolonged exposure of cells to TPA did not affect LAP-induced tyrosine phosphorylation of SHPS-1. LPA-induced tyrosine phosphorylation of SHPS-1 was markedly reduced in either focal adhesion kinase (FAK)-deficient mouse cells or CHO cells overexpressing the tyrosine kinase CSK. Overexpression of a catalytically inactivate SHP-2 markedly inhibited MAP kinase activation in response to low concentrations of LPA in CHO cells, whereas overexpression of a wild-type SHPS-1 did enhance this effect of LPA. Furthermore, MAP kinase activation in response to a low concentration of LPA was inhibited by botulinum C3 exoenzyme. These results indicate that LPA-induced tyrosine phosphorylation of SHPS-1 and its association with SHP-2 may be mediated by a RHO-dependent pathway that includes FAK and a SRC family kinase. Thus, in addition to its role in receptor tyrosine kinase-mediated MAP kinase activation, the formation of a complex between SHPS-1 and SHP-2 may, in part, play an important role in the activation of MAP kinase in response to low concentrations of LPA.

ADP Ribose Transferases↗