دورية أكاديمية
Phosphatidylinositol 3-kinase-dependent translocation of phospholipase Cgamma2 in mouse megakaryocytes is independent of Bruton tyrosine kinase translocation.
العنوان: | Phosphatidylinositol 3-kinase-dependent translocation of phospholipase Cgamma2 in mouse megakaryocytes is independent of Bruton tyrosine kinase translocation. |
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المؤلفون: | Bobe R; Department of Pharmacology, University of Oxford, United Kingdom. regis.bobe@pharm.ox.ac.uk, Wilde JI, Maschberger P, Venkateswarlu K, Cullen PJ, Siess W, Watson SP |
المصدر: | Blood [Blood] 2001 Feb 01; Vol. 97 (3), pp. 678-84. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 7603509 Publication Model: Print Cited Medium: Print ISSN: 0006-4971 (Print) Linking ISSN: 00064971 NLM ISO Abbreviation: Blood Subsets: MEDLINE |
أسماء مطبوعة: | Publication: 2021- : [New York] : Elsevier Original Publication: New York, Grune & Stratton [etc.] |
مواضيع طبية MeSH: | Carrier Proteins*, Isoenzymes/*metabolism , Megakaryocytes/*enzymology , Phosphatidylinositol 3-Kinases/*physiology , Protein-Tyrosine Kinases/*metabolism , Type C Phospholipases/*metabolism, Agammaglobulinaemia Tyrosine Kinase ; Agammaglobulinemia/enzymology ; Androstadienes/pharmacology ; Animals ; Blood Platelets/drug effects ; Blood Platelets/enzymology ; Calcium/metabolism ; Cell Membrane/drug effects ; Cell Membrane/metabolism ; Cells, Cultured ; Enzyme Inhibitors/pharmacology ; Enzyme Precursors/metabolism ; Humans ; Intracellular Signaling Peptides and Proteins ; Isoenzymes/chemistry ; Megakaryocytes/drug effects ; Mice ; Mice, Mutant Strains ; Models, Biological ; Phosphatidylinositol Phosphates/metabolism ; Phosphoinositide-3 Kinase Inhibitors ; Phospholipase C gamma ; Protein Transport ; Proteins/pharmacology ; Syk Kinase ; Thrombin/pharmacology ; Type C Phospholipases/chemistry ; Wortmannin ; X Chromosome ; src Homology Domains |
مستخلص: | Activation of the collagen receptor glycoprotein VI (GPVI) by a collagen-related peptide (CRP) induces stimulation of platelets and megakaryocytes through the phosphatidylinositol (PI) 3-kinase-dependent pathway leading to activation of Bruton tyrosine kinase (Btk) and phospholipase Cgamma2 (PLCgamma2). Here, we present evidence that both proteins undergo PI 3-kinase-dependent translocation to the plasma membrane on CRP stimulation that is markedly inhibited by wortmannin and LY294002. Translocation of PLCgamma2 but not Btk is also seen in megakaryocytes from X-linked immunodeficiency mice, which have a mutation that reduces the affinity of the pleckstrin homology (PH) domain of Btk for PI 3,4,5-trisphosphate (PI 3,4,5-P3). Activation of PC12 cells by epidermal growth factor (EGF) results in increased PI 3-kinase activity and high PI 3,4,5-P3 levels that trigger translocation of the green fluorescent protein (GFP)-labeled PH of Btk, but not the GFP-labeled PH and tandem Src homology 2 (SH2) domains of PLCgamma2. In contrast to the results with CRP, the G protein-coupled receptor agonist thrombin stimulates PI 3-kinase-independent translocation of Btk but not PLCgamma2. In conclusion, these results demonstrate that in mouse megakaryocytes, CRP leads to PI 3-kinase-dependent translocation of PLCgamma2 and Btk that are independent of one another, whereas thrombin only induces translocation of Btk through a pathway that is independent of PI 3-kinase activity. |
المشرفين على المادة: | 0 (Androstadienes) 0 (Carrier Proteins) 0 (Enzyme Inhibitors) 0 (Enzyme Precursors) 0 (Intracellular Signaling Peptides and Proteins) 0 (Isoenzymes) 0 (Phosphatidylinositol Phosphates) 0 (Phosphoinositide-3 Kinase Inhibitors) 0 (Proteins) 0 (c1q-binding proteins) 0 (phosphatidylinositol 3,4,5-triphosphate) EC 2.7.10.1 (Protein-Tyrosine Kinases) EC 2.7.10.2 (Agammaglobulinaemia Tyrosine Kinase) EC 2.7.10.2 (BTK protein, human) EC 2.7.10.2 (Btk protein, mouse) EC 2.7.10.2 (SYK protein, human) EC 2.7.10.2 (Syk Kinase) EC 2.7.10.2 (Syk protein, mouse) EC 3.1.4.- (Type C Phospholipases) EC 3.1.4.3 (Phospholipase C gamma) EC 3.4.21.5 (Thrombin) SY7Q814VUP (Calcium) XVA4O219QW (Wortmannin) |
تواريخ الأحداث: | Date Created: 20010207 Date Completed: 20010315 Latest Revision: 20210216 |
رمز التحديث: | 20221213 |
DOI: | 10.1182/blood.v97.3.678 |
PMID: | 11157484 |
قاعدة البيانات: | MEDLINE |
تدمد: | 0006-4971 |
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DOI: | 10.1182/blood.v97.3.678 |