Anti‐CD9 monoclonal antibody elicits staurosporine inhibitable phosphatidylinositol 4,5‐bisphosphate hydrolysis, phosphatidylinositol 3,4‐bisphosphate synthesis, and protein‐tyrosine phosphorylation in human platelets

Yatomi, Yutaka; Yukio, Ozaki; Satoh, Kaneo; Kudoh, Shoji

doi:10.1016/0014-5793(93)81587-p

Cited by 29 publications

(22 citation statements)

References 48 publications

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“…The precise physiological functions of CD9 remain unknown. However, several studies have suggested that CD9 may be involved in cell signaling, 45,46 cell adhesion, 28,29 cell motility, 47 tumor cell metastasis. 42-44,48 -51 Clinical studies on the expression of CD9 in human cancer tissues have shown a the relationship between the reduced expression of CD9 and the aggressive behavior of the tumor.…”

Section: Discussionmentioning

confidence: 99%

Significance of the association between heparin‐binding epidermal growth factor‐like growth factor and CD9 in human gastric cancer

Murayama

Miyagawa

Shinomura

et al. 2002

Intl Journal of Cancer

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Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member of the EGF family. Juxtacrine activity of proHB-EGF (the membrane-anchored form of HB-EGF) has been shown to be significantly potentiated when it is coexpressed with CD9 in vitro. The purpose of our study was to investigate the issue of whether proHB-EGF and CD9 are coexpressed in gastric cancer. HB-EGF gene expression and protein production in human gastric cancers was investigated, and EGF receptor and CD9 expressions were also evaluated. HB-EGF mRNA levels in gastric cancers were elevated, compared with normal gastric tissues, especially in the intestinal type. ProHB-EGF immunoreactivity was detected primarily in the cytoplasm and plasma membrane of gastric cancer cells. Of 66 patients, 40 (60.6%) exhibited proHB-EGF immunoreactivity and the level of its expression was significantly associated with tumor status (p < 0.01) and histological differentiation (p < 0.001). In addition, proHB-EGF mRNA was detected at high levels in the intestinal type by in situ hybridization. CD9 immunoreactivity was found to be preserved in 26 of 36 patients (72.2%) and CD9 protein expression was inversely associated with lymph node status (p < 0.05). A significant correlation between its expression and histological differentiation (p < 0.01) was found, and the association of CD9 with proHB-EGF was increased in the intestinal type, as evidenced by an immunoprecipitation method. These results indicate that the coexpression of proHB-EGF and CD9 may be involved in the tumorigenesis and/or proliferation of gastric cancers in a juxtacrine manner.

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Section: Discussionmentioning

confidence: 99%

Significance of the association between heparin‐binding epidermal growth factor‐like growth factor and CD9 in human gastric cancer

Murayama

Miyagawa

Shinomura

et al. 2002

Intl Journal of Cancer

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“…Although the specific functional role of the tetramembranespanning family is not fully defined, members of this family appear to associate with adhesion molecules and translate adhesive events into a regulation of cellular behavior (Yatomi et al, 1993). One family member, KAI1, is a metastatic suppressor for prostate cancer (Dong et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

“…The roles of CD9 in regulating adhesion and cell growth are reflected in its noncovalent association with ␤1 integrin, an adhesion molecule (Slupsky et al, 1989;Masellis-Smith and Shaw, 1994), and membraneanchored EGF-like growth factors (Nakamura et al, 1995). Furthermore, activation of CD9 is associated with the hydrolysis of phosphoinositide during platelet activation (Jennings et al, 1990;Yatomi et al, 1993). Another member of the family, TAPA-1, is found in hematolymphoid cells.…”

Section: Discussionmentioning

confidence: 99%

Astrocyte Growth, Reactivity, and the Target of the Antiproliferative Antibody, TAPA

1996

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Reactive astrocytes form a scar after injury to the CNS that many investigators believe contributes to the lack of functional regeneration. In the present study, we identify an astrocytic membrane protein that appears to play an important role in reactive gliosis and scar formation. Cultures of rat astrocytes were used as a model system to produce and to screen monoclonal antibodies that would alter cell growth. One antibody, AMP1, was identified that depresses the mitotic activity of cultured glial cells and alters their morphology. Expression cloning reveals that the antigen on the external surface of the cultured glial cells has a high degree of homology with the human lymphocyte protein called Target of the Anti-Proliferative Antibody (TAPA-1; this rat protein will be referred to as rTAPA). rTAPA is a member of the tetramembrane-spanning superfamily of proteins and, as with other members of this family of proteins, rTAPA is associated with the regulation of cellular interactions and mitotic activity. After an injury to the cerebral cortex, there is a dramatic increase in AMP1 immunoreactivity that is spatially restricted to the reactive astrocytes at the glial scar. This change represents an upregulation of a membrane protein, rTAPA, that is approximately equal to the increase observed for glial fibrillary acidic protein. The high levels of rTAPA at the site of CNS injury and the AMP1 antibody perturbation studies indicate that rTAPA may play a prominent role in the response of astrocytes to injury and in glial scar formation.

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“…There is evidence that PIP2 hydrolysis in platelets may also be mediated by a tyrosine kinase-activated phospholipase C-gamma [17]. However it is unlikely that staurosporine activated this pathway since it inhibits tyrosine kinase activities [ 171.…”

Section: Discussionmentioning

confidence: 99%

Staurosporine induces hydrolysis of phosphatidyl inositol 4,5‐bisphosphate in human platelets

Turkson

Wong

1994

FEBS Letters

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Staurosporine in the micromolar range raised inositol trisphosphate in intact human platelets to levels comparable to that mediated by thrombin. This response was inhibited by neomycin, a phospholipase C antagonist. Staurosporine alone induced a weak, transient rise in cytosolic free calcium levels ([Ca2']J from release of internal Ca*+ stores but potentiated the effect induced by thrombin. Therefore, it is unlikely that this alkaloid suppressed inositol trisphosphate mobilization of Ca2'. Additional studies show that staurosporine, OS-5 ,uM, stimulated GTPase activity in platelet membranes while 2 PM K252a and 20 FM H7 were inactive. Present results suggest that staurosporine may activate platelet phospholipase C at the level of G proteins or receptors. Key wor& Staurosporine;Platelet; Phospholipa~ C; Calcium; Inositol phosphate _ _ lntrodwtionStaurosporine, a microbial alkaloid from Streptomyces sp. is a potent but nonspecific inhibitor of protein kinase C (PI(C) (IC,, of 3 nM) [l]. This reagent has been used in numerous studies to inhibit PKC-dependent responses in platelets [3-61. Recently we showed that staurosporine in the micromolar range causes a rapid and sustained elevation of cytosolic free Ca" concentration ([Ca"+]J in neutrophils via an indirect mechanism [7f. Subsequently, Himpens and coworkers [S] reported that staurosporine mobilizes intra~ll~ar Ca" stores and induces Ca2' influx in cultured DDTlMF-2 smooth muscle cells. In both studies, the effect of staurosporine on [Ca2']i is not correlated with PKC inhibition or phospholipase C (PLC) activation. The present study was undertaken to investigateand compare the effect of staurosporine on [Ca2']i in human platelets. We report here that micromolar staurosporine induced significant hydrolysis of phosphatidyl inositol4,5-bisphosphate (PIP2) but weak transient elevations of [Ca2'J,. Materials and methods Materials['H]Myo-inositol, (W-120 Ciimmol) and a ligand binding assay kit for Ins(1,4,5)P, were from Amersham Canada Ltd. (Oakville, Qnt.); human thrombin, apyrase, neomycin sulfate, and prostacyclin were from Sigma Chemical Co. (St. Louis, MO); staurosporine was obtained from Sigma and Boehringer Mannheim (Montreal, P.Q.); Fura-AM and ionomycin were from Calbiochem Corp. (San Diego, CA); Stock solutions of staurosporine and ionomycin were dissolved in dimethyl sulfoxide (MesSO) and stored at -80°C. separation of platelet ~pe~~nBlood was drawn by ve~p~cture from drug-free volunteers into 116 volume acid citrate dextrose. Platelet-rich plasma was obtained by centrifuging whole blood at 300 x g at room temperature for 15 min. After careful removal, the plasma was further centrifuged at 2500 x g at room temperature for 10 min to pellet the platelets. Platelets were resuspended in Tyrode-HEPES buffer (134 mM NaCl, 12 mM NaHCO,, 2.9 mM KCl, 0.36 mM NaH,PQ4, 1 mM MgCl,, 5 mM HEPES,J mM glucose; pH 7.2) containing apyrase (0.6 ADPase U/ml) and 0.35% bovine serum albumin. For labeling platelets with [3H]myoinositol, the buffer also contained 1 mM EG...

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Anti‐CD9 monoclonal antibody elicits staurosporine inhibitable phosphatidylinositol 4,5‐bisphosphate hydrolysis, phosphatidylinositol 3,4‐bisphosphate synthesis, and protein‐tyrosine phosphorylation in human platelets

Cited by 29 publications

References 48 publications

Significance of the association between heparin‐binding epidermal growth factor‐like growth factor and CD9 in human gastric cancer

Significance of the association between heparin‐binding epidermal growth factor‐like growth factor and CD9 in human gastric cancer

Astrocyte Growth, Reactivity, and the Target of the Antiproliferative Antibody, TAPA

Staurosporine induces hydrolysis of phosphatidyl inositol 4,5‐bisphosphate in human platelets

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