Phosphatidylinositol 3-kinase-dependent translocation of phospholipase C gamma 2 in mouse megakaryocytes is independent of Bruton tyrosine kinase translocation
R. Bobe et al., Phosphatidylinositol 3-kinase-dependent translocation of phospholipase C gamma 2 in mouse megakaryocytes is independent of Bruton tyrosine kinase translocation, BLOOD, 97(3), 2001, pp. 678-684
Activation of the collagen receptor glycoprotein VI (GPVI) by a collagen-re
lated peptide (CRP) induces stimulation of platelets and megakaryocytes thr
ough the phosphatidylinositol (PI) 3-kinase-dependent pathway leading to ac
tivation of Bruton tyrosine kinase (Btk) and phospholipase C gamma2 (PLC ga
mma2), Here, we present evidence that both proteins undergo PI 3-kinase-dep
endent translocation to the plasma membrane on CRP stimulation that is mark
edly inhibited by wortmannin and LY294002, Translocation of PLC gamma2 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-kina
se activity and high PI 3,4,5-P3 levels that trigger translocation of the g
reen fluorescent protein (GFP)-labeled PH of Btk, but not the GFP-labeled P
H and tandem Src homology 2 (SH2) domains of PLC gamma2, In contrast to the
results with CRP, the G protein-coupled receptor agonist thrombin stimulat
es PI 3-kinase-independent translocation of Btk but not PLC gamma2, In conc
lusion, these results demonstrate that in mouse megakaryocytes, CRP leads t
o PI 3-kinase-dependent translocation of PLC gamma2 and Btk that are indepe
ndent of one another, whereas thrombin only induces translocation of Btk th
rough a pathway that is independent of PI 3-kinase activity. (C) 2001 by Th
e American Society of Hematology.