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© The Rockefeller University Press,
0021-9525/2001//361 $5.00
The Journal of Cell Biology, Volume 152, Number 2,
, 2001 361-374
Original Article |
Convergence of
vβ3Integrin–And Macrophage Colony Stimulating Factor–Mediated Signals on Phospholipase C
in Prefusion Osteoclasts
le_duong{at}merck.com
The macrophage colony stimulating factor (M-CSF) and
vβ3 integrins play critical roles in osteoclast function. This study examines M-CSF– and adhesion-induced signaling in prefusion osteoclasts (pOCs) derived from Src-deficient and wild-type mice. Src-deficient cells attach to but do not spread on vitronectin (Vn)-coated surfaces and, contrary to wild-type cells, their adhesion does not lead to tyrosine phosphorylation of molecules activated by adhesion, including PYK2, p130Cas, paxillin, and PLC-
. However, in response to M-CSF, Src–/– pOCs spread and migrate on Vn in an
vβ3-dependent manner. Involvement of PLC-
activation is suggested by using a PLC inhibitor, U73122, which blocks both adhesion- and M-CSF–mediated cell spreading. Furthermore, in Src–/– pOCs M-CSF, together with filamentous actin, causes recruitment of β3 integrin and PLC-
to adhesion contacts and induces stable association of β3 integrin with PLC-
, phosphatidylinositol 3-kinase, and PYK2. Moreover, direct interaction of PYK2 and PLC-
can be induced by either adhesion or M-CSF, suggesting that this interaction may enable the formation of integrin-associated complexes. Furthermore, this study suggests that in pOCs PLC-
is a common downstream mediator for adhesion and growth factor signals. M-CSF–initiated signaling modulates the
vβ3 integrin-mediated cytoskeletal reorganization in prefusion osteoclasts in the absence of c-Src, possibly via PLC-
.
Key Words:
vβ3 integrins osteoclasts M-CSF Src kinases phospholipase C
© 2001 The Rockefeller University Press
Abbreviations used in this paper: ECM, extracellular matrix; ERK, extracellular signal–regulated kinase; FAK, focal adhesion kinase; GST, glutathione S-transferase; MAP, mitogen-activated protein; M-CSF, macrophage colony stimulating factor; OCL, multinucleated osteoclast-like cell; PI 3-kinase, phosphatidylinositol 3-kinase; PL, poly-L-lysine; pOC, prefusion osteoclast-like cell; SH, src homology; TRAP, tartrate-resistant acid phosphatase; Vn, vitronectin.
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