Gene interactions and pathways from curated databases and text-mining
J Immunol 2009, PMID: 19592646

SLP-76 couples Syk to the osteoclast cytoskeleton.

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

  • Reactome Reaction: GRAP2 → IGLC3 (reaction)
  • Reactome Reaction: IGHE → SOS1 (reaction)
  • 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)
  • 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)
  • Reactome Reaction: SYK → LAT (reaction)
  • Reactome Reaction: PLCG2 → IGLC1 (reaction)
  • 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