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Phosphatidylinositol 3-kinase-dependent translocation of phospholipase Cgamma2 in mouse megakaryocytes is independent of Bruton tyrosine kinase translocation.
- Source :
-
Blood [Blood] 2001 Feb 01; Vol. 97 (3), pp. 678-84. - Publication Year :
- 2001
-
Abstract
- 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.
- Subjects :
- 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
Carrier Proteins
Isoenzymes metabolism
Megakaryocytes enzymology
Phosphatidylinositol 3-Kinases physiology
Protein-Tyrosine Kinases metabolism
Type C Phospholipases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0006-4971
- Volume :
- 97
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 11157484
- Full Text :
- https://doi.org/10.1182/blood.v97.3.678