Molecules and Cells

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Fig. 2.

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Fig. 2. RANK signaling cooperates with immunoglobulin-like receptor/ITAM signals such as TREM-2/DAP12 and OSCAR/FcRγ, thereby leading to the amplification and translocation of NFATc1. When ITAM is tyrosine phosphorylated, Btk/Tec and BLNK/SLP-76 form a complex with PLCγ2 to activate PLCγ2 and Ca2+ signaling. EEIG1 induced by NFATc1 associates with Gab2 via the IVVY motif in RANK and then activates Btk/Tec followed by PLCγ2, suggesting that EEIG1 integrates RANK and ITAM signaling. Ca2+ oscillation induces calmodulin and calcineurin activation to regulate the nuclear translocation and amplification of NFATc1. The subcellular localization of NFATc1 is influenced by the phosphorylation of serine residues regulated by Gsk-3β, which is inhibited by either PI3K-Akt signaling or PKCβ. ITAM, immunoreceptor tyrosine-based activation motif; TREM-2, triggering receptor expressed in myeloid cells-2; DAP12, DNAX-activation protein 12; OSCAR, osteoclast-associated receptor; FcRγ, Fc receptor common γ subunit; Btk, Bruton’s tyrosine kinase; BLNK, B cell linker protein; SLP-76, Src homology 2 domain-containing leukocyte protein of 76 kD; EEIG1, early estrogen-induced gene 1; Gsk-3β, Glycogen synthase kinase-3β; PI3K, phosphoinositide 3-kinase; PKCβ, protein kinase Cβ.
Mol. Cells 2017;40:706~713
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