J Immunol 2009,
PMID: 19592646
Reeve, Jennifer L; Zou, Wei; Liu, Yuli; Maltzman, Jonathan S; Ross, F Patrick; Teitelbaum, Steven L
The capacity of the osteoclast (OC) to resorb bone is dictated by cytoskeletal organization, which in turn emanates from signals derived from the alpha(v)beta(3) integrin and c-Fms. Syk is key to these signals and, in other cells, this tyrosine kinase exerts its effects via intermediaries including the SLP adaptors, SLP-76 and BLNK (B cell linker). Thus, we asked whether these two SLP proteins regulate OC function. We find BLNK-deficient OCs are normal, whereas cytoskeletal organization of those lacking SLP-76 is delayed, thus modestly reducing bone resorption in vitro. Cytoskeletal organization and bone resorption are more profoundly arrested in cultured OCs deficient in BLNK and SLP-76 double knockout (DKO) phenotypes. In contrast, stimulated bone resorption in vivo is inhibited approximately 40% in either SLP-76(-/-) or DKO mice. This observation, taken with the fact that DKO OCs are rescued by retroviral transduction of only SLP-76, indicates that SLP-76 is the dominant SLP family member in the resorptive process. We also find SLP-76 is phosphorylated in a Syk-dependent manner. Furthermore, in the absence of the adaptor protein, integrin-mediated phosphorylation of Vav3, the OC cytoskeleton-organizing guanine nucleotide exchange factor, is abrogated. In keeping with a central role of SLP-76/Vav3 association in osteoclastic resorption, retroviral transduction of SLP-76, in which the Vav binding site is disrupted (3YF), fails to normalize the cytoskeleton of DKO OCs and the resorptive capacity of the cells. Finally, c-Fms-activated Syk also exerts its OC cytoskeleton-organizing effect in a SLP-76/Vav3-dependent manner.
Diseases/Pathways annotated by Medline MESH: Bone Resorption
Document information provided by NCBI PubMed
Text Mining Data
SLP-76 — Syk: "
We also find
SLP-76 is phosphorylated in a
Syk dependent manner
"
Syk → c-Fms: "
Finally, c-Fms activated Syk also exerts its OC cytoskeleton organizing effect in a SLP-76/Vav3 dependent manner
"
Manually curated Databases
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Reactome Reaction:
GRAP2
→
IGLC3
(reaction)
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Reactome Reaction:
IGHE
→
SOS1
(reaction)
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Reactome Reaction:
IGKV1-5
→
SOS1
(reaction)
-
Reactome Reaction:
GRB2
→
HLA-E
(reaction)
-
Reactome Reaction:
KLRC2
→
LAT
(reaction)
-
Reactome Reaction:
IGKV4-1
→
PLCG1
(reaction)
-
Reactome Reaction:
FYN
→
PLCG2
(reaction)
-
Reactome Reaction:
B2M
→
PLCG2
(reaction)
-
Reactome Reaction:
KLRK1
→
SOS1
(reaction)
-
Reactome Reaction:
LCP2
→
SHC1
(indirect_complex)
-
Reactome Reaction:
GRB2
→
IGLC2
(reaction)
-
Reactome Reaction:
LYN
→
SOS1
(reaction)
-
Reactome Reaction:
GRAP2
→
KLRC2
(reaction)
-
Reactome Reaction:
GRB2
→
IGLC6
(reaction)
-
Reactome Reaction:
LCP2
→
KLRC2
(reaction)
-
Reactome Reaction:
LCP2
→
PLCG2
(indirect_complex)
-
Reactome Reaction:
IGKV4-1
→
PLCG2
(reaction)
-
Reactome Reaction:
IGKV4-1
→
SOS1
(reaction)
-
Reactome Reaction:
SHC1
→
IGLC1
(reaction)
-
Reactome Reaction:
IGKC
→
PLCG2
(reaction)
-
Reactome Reaction:
B2M
→
LAT
(reaction)
-
Reactome Reaction:
PLCG1
→
IGLC7
(reaction)
-
Reactome Reaction:
LYN
→
PLCG2
(reaction)
-
Reactome Reaction:
B2M
→
SHC1
(reaction)
-
Reactome Reaction:
LYN
→
SHC1
(reaction)
-
Reactome Reaction:
LCK
→
LCP2
(reaction)
-
Reactome Reaction:
GRB2
→
KLRK1
(reaction)
-
Reactome Reaction:
PLCG2
→
IGLC3
(reaction)
-
Reactome Reaction:
SHC1
→
IGLC7
(reaction)
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Reactome Reaction:
SYK
→
PLCG1
(reaction)
-
Reactome Reaction:
LCP2
→
LAT
(indirect_complex)
-
Reactome Reaction:
LCK
→
PLCG2
(reaction)
-
Reactome Reaction:
IGHE
→
GRAP2
(reaction)
-
Reactome Reaction:
LCK
→
PLCG1
(reaction)
-
Reactome Reaction:
FYN
→
LAT
(reaction)
-
Reactome Reaction:
IGHE
→
SHC1
(reaction)
-
Reactome Reaction:
IGKC
→
LCP2
(reaction)
-
Reactome Reaction:
LAT
→
TREM2
(reaction)
-
Reactome Reaction:
LAT
→
IGLC6
(reaction)
-
Reactome Reaction:
GRAP2
→
IGLC2
(reaction)
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Reactome Reaction:
SYK
→
LAT
(reaction)
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Reactome Reaction:
PLCG2
→
IGLC1
(reaction)
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Reactome Reaction:
PLCG1
→
TREM2
(reaction)
-
Reactome Reaction:
GRB2
→
KLRC2
(reaction)
-
Reactome Reaction:
LCP2
→
SOS1
(indirect_complex)
-
Reactome Reaction:
GRB2
→
KLRD1
(reaction)
-
Reactome Reaction:
B2M
→
SOS1
(reaction)
-
Reactome Reaction:
IGHE
→
GRB2
(reaction)
-
Reactome Reaction:
KLRK1
→
PLCG2
(reaction)
-
Reactome Reaction:
IGHE
→
PLCG2
(reaction)
-
Reactome Reaction:
PLCG2
→
KLRD1
(reaction)
-
Reactome Reaction:
FYN
→
SOS1
(reaction)
-
Reactome Reaction:
B2M
→
GRB2
(reaction)
-
Reactome Reaction:
IGKV1-5
→
LCP2
(reaction)
-
Reactome Reaction:
SOS1
→
IGLC7
(reaction)
-
Reactome Reaction:
HLA-E
→
PLCG2
(reaction)
-
Reactome Reaction:
PLCG2
→
SHC1
(indirect_complex)
-
Reactome Reaction:
GRAP2
→
PLCG2
(indirect_complex)
-
Reactome Reaction:
LAT
→
IGLC1
(reaction)
-
Reactome Reaction:
PLCG2
→
IGLC6
(reaction)
-
Reactome Reaction:
GRAP2
→
IGKV4-1
(reaction)
-
Reactome Reaction:
IGKV1-5
→
PLCG2
(reaction)
-
Reactome Reaction:
HLA-E
→
LAT
(reaction)
-
Reactome Reaction:
TYROBP
→
SHC1
(reaction)
-
Reactome Reaction:
FYN
→
SHC1
(reaction)
-
Reactome Reaction:
SHC1
→
IGLC3
(reaction)
-
Reactome Reaction:
IGHE
→
LAT
(reaction)
-
Reactome Reaction:
HLA-E
→
LCP2
(reaction)
-
Reactome Reaction:
LAT
→
KLRD1
(reaction)
-
Reactome Reaction:
LCK
→
SOS1
(reaction)
-
Reactome Reaction:
PLCG2
→
IGLC2
(reaction)
-
Reactome Reaction:
FYN
→
GRB2
(reaction)
-
Reactome Reaction:
HLA-E
→
PLCG1
(reaction)
-
Reactome Reaction:
LCP2
→
LYN
(reaction)
-
Reactome Reaction:
SOS1
→
IGLC3
(reaction)
-
Reactome Reaction:
GRB2
→
IGKV1-5
(reaction)
-
Reactome Reaction:
GRAP2
→
LCK
(reaction)
-
Reactome Reaction:
PLCG1
→
SOS1
(indirect_complex)
-
Reactome Reaction:
IGKV4-1
→
LAT
(reaction)
-
Reactome Reaction:
GRAP2
→
LYN
(reaction)
-
Reactome Reaction:
IGKV4-1
→
LCP2
(reaction)
-
Reactome Reaction:
B2M
→
LCP2
(reaction)
-
Reactome Reaction:
SOS1
→
IGLC2
(reaction)
-
Reactome Reaction:
GRAP2
→
IGLC7
(reaction)
-
Reactome Reaction:
SYK
→
SOS1
(reaction)
-
Reactome Reaction:
KLRC2
→
SOS1
(reaction)
-
Reactome Reaction:
LAT
→
IGLC2
(reaction)
-
Reactome Reaction:
GRAP2
→
TREM2
(reaction)
-
Reactome Reaction:
IGKV1-5
→
PLCG1
(reaction)
-
Reactome Reaction:
LCP2
→
KLRD1
(reaction)
-
Reactome Reaction:
PLCG1
→
LAT
(indirect_complex)
-
Reactome Reaction:
GRAP2
→
IGKV1-5
(reaction)
-
Reactome Reaction:
GRB2
→
IGKC
(reaction)
-
Reactome Reaction:
IGKV1-5
→
LAT
(reaction)
-
Reactome Reaction:
SHC1
→
IGLC2
(reaction)
-
Reactome Reaction:
SOS1
→
KLRD1
(reaction)
-
Reactome Reaction:
PLCG2
→
SOS1
(indirect_complex)
-
Reactome Reaction:
SHC1
→
IGLC6
(reaction)
-
Reactome Reaction:
FYN
→
GRAP2
(reaction)
-
Reactome Reaction:
GRB2
→
IGLC7
(reaction)
-
Reactome Reaction:
LCK
→
LAT
(reaction)
-
Reactome Reaction:
B2M
→
PLCG1
(reaction)
-
Reactome Reaction:
GRAP2
→
IGKC
(reaction)
-
Reactome Reaction:
FYN
→
PLCG1
(reaction)
-
Reactome Reaction:
B2M
→
GRAP2
(reaction)
-
Reactome Reaction:
TREM2
→
SHC1
(reaction)
-
Reactome Reaction:
LCP2
→
PLCG1
(indirect_complex)
-
Reactome Reaction:
LCP2
→
IGLC7
(reaction)
-
Reactome Reaction:
SYK
→
PLCG2
(reaction)
-
Reactome Reaction:
SOS1
→
TYROBP
(reaction)
-
Reactome Reaction:
PLCG1
→
IGLC6
(reaction)
-
Reactome Reaction:
IGKC
→
PLCG1
(reaction)
-
Reactome Reaction:
LCP2
→
TYROBP
(reaction)
-
Reactome Reaction:
GRB2
→
SYK
(reaction)
-
Reactome Reaction:
GRAP2
→
KLRD1
(reaction)
-
Reactome Reaction:
LYN
→
PLCG1
(reaction)
-
Reactome Reaction:
SYK
→
SHC1
(reaction)
-
Reactome Reaction:
GRB2
→
IGLC1
(reaction)
-
Reactome Reaction:
GRB2
→
LCK
(reaction)
-
Reactome Reaction:
GRAP2
→
LAT
(indirect_complex)
-
Reactome Reaction:
LCP2
→
IGLC1
(reaction)
-
Reactome Reaction:
GRB2
→
IGKV4-1
(reaction)
-
Reactome Reaction:
LCP2
→
TREM2
(reaction)
-
Reactome Reaction:
SHC1
→
KLRD1
(reaction)
-
Reactome Reaction:
SYK
→
LCP2
(reaction)
-
Reactome Reaction:
HLA-E
→
SOS1
(reaction)
-
Reactome Reaction:
IGKV4-1
→
SHC1
(reaction)
-
Reactome Reaction:
HLA-E
→
SHC1
(reaction)
-
Reactome Reaction:
GRB2
→
TYROBP
(reaction)
-
Reactome Reaction:
GRAP2
→
IGLC1
(reaction)
-
Reactome Reaction:
TYROBP
→
LAT
(reaction)
-
Reactome Reaction:
KLRC2
→
PLCG1
(reaction)
-
Reactome Reaction:
LAT
→
IGLC3
(reaction)
-
Reactome Reaction:
IGKC
→
SHC1
(reaction)
-
Reactome Reaction:
KLRK1
→
PLCG1
(reaction)
-
Reactome Reaction:
KLRK1
→
LAT
(reaction)
-
Reactome Reaction:
GRAP2
→
SYK
(reaction)
-
Reactome Reaction:
IGKC
→
LAT
(reaction)
-
Reactome Reaction:
LYN
→
LAT
(reaction)
-
Reactome Reaction:
GRAP2
→
HLA-E
(reaction)
-
Reactome Reaction:
GRAP2
→
KLRK1
(reaction)
-
Reactome Reaction:
IGKC
→
SOS1
(reaction)
-
Reactome Reaction:
FYN
→
LCP2
(reaction)
-
Reactome Reaction:
KLRC2
→
PLCG2
(reaction)
-
Reactome Reaction:
GRB2
→
GRAP2
(indirect_complex)
-
Reactome Reaction:
PLCG1
→
IGLC2
(reaction)
-
Reactome Reaction:
LAT
→
IGLC7
(reaction)
-
Reactome Reaction:
GRB2
→
LCP2
(indirect_complex)
-
Reactome Reaction:
LCP2
→
IGLC3
(reaction)
-
Reactome Reaction:
GRB2
→
IGLC3
(reaction)
-
Reactome Reaction:
PLCG1
→
TYROBP
(reaction)
-
Reactome Reaction:
GRAP2
→
PLCG1
(indirect_complex)
-
Reactome Reaction:
PLCG1
→
IGLC3
(reaction)
-
Reactome Reaction:
PLCG1
→
IGLC1
(reaction)
-
Reactome Reaction:
IGHE
→
LCP2
(reaction)
-
Reactome Reaction:
LCP2
→
IGLC6
(reaction)
-
Reactome Reaction:
SOS1
→
TREM2
(reaction)
-
Reactome Reaction:
PLCG2
→
LAT
(indirect_complex)
-
Reactome Reaction:
PLCG1
→
KLRD1
(reaction)
-
Reactome Reaction:
PLCG2
→
IGLC7
(reaction)
-
Reactome Reaction:
LCK
→
SHC1
(reaction)
-
Reactome Reaction:
IGKV1-5
→
SHC1
(reaction)
-
Reactome Reaction:
LCP2
→
IGLC2
(reaction)
-
Reactome Reaction:
KLRK1
→
SHC1
(reaction)
-
Reactome Reaction:
PLCG2
→
TREM2
(reaction)
-
Reactome Reaction:
LCP2
→
KLRK1
(reaction)
-
Reactome Reaction:
KLRC2
→
SHC1
(reaction)
-
Reactome Reaction:
GRB2
→
TREM2
(reaction)
-
Reactome Reaction:
GRAP2
→
SOS1
(indirect_complex)
-
Reactome Reaction:
SOS1
→
IGLC1
(reaction)
-
Reactome Reaction:
GRAP2
→
SHC1
(indirect_complex)
-
Reactome Reaction:
PLCG1
→
SHC1
(indirect_complex)
-
Reactome Reaction:
IGHE
→
PLCG1
(reaction)
-
Reactome Reaction:
PLCG2
→
TYROBP
(reaction)
-
Reactome Reaction:
GRAP2
→
IGLC6
(reaction)
-
Reactome Reaction:
GRB2
→
LYN
(reaction)
-
Reactome Reaction:
GRAP2
→
TYROBP
(reaction)
-
Reactome Reaction:
GRB2
→
PLCG1
(indirect_complex)
-
Reactome Reaction:
SOS1
→
IGLC6
(reaction)
-
Reactome Reaction:
GRB2
→
PLCG2
(indirect_complex)
In total, 180 gene pairs are associated to this article in curated databases