hematopoietic cell signal transducer (transmembrane adapter protein KAP10, DNAX-activation protein 10, membrane protein DAP10, HCST, DAP10, KAP10, PIK3AP, UNQ587/PRO1157)

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Function

transmembrane adapter protein
associates with NKG2D to form an activation receptor NKG2D-HCST in lymphoid & myeloid cells
- this receptor plays a major role in triggering cytotoxicity against target cells expressing cell surface ligands such as MHC class I chain-related MICA & MICB, & UL16-binding proteins (ULBPs)
- these ligands are up-regulated by stress conditions & pathological state such as viral infection & tumor transformation.
functions as docking site for PI3-kinase PIK3R1 & GRB2
interaction of ULBPs with NKG2D-DAP10 triggers Ca+2 mobilization & activation of the PIK3R1, MAP2K/ERK, & JAK2/STAT5 signaling pathways
both PIK3R1 & GRB2 are required for full NKG2D-HCST-mediated activation & ultimate killing of target cells.
in NK cells, NKG2D-HCST signaling directly induces cytotoxicity & enhances cytokine production initiated via DAP12/TYROBP-associated receptors
in T cells, it provides primarily costimulation for TCR-induced signals
NKG2D-HCST receptor plays a role in immune surveillance against tumors & is required for cytolysis of tumors cells; melanoma cells that do not express NKG2D ligands escape from immune surveillance mediated by NK cells
interacts with NKG2D to form a stable complex, which results in surface expression of both proteins, whereas alone, it is minimally expressed
interacts with PIK3R1 & GRB2
phosphorylated; PIK3R1 & GRB2 associate specifically with tyrosine-phosphorylated HCST

membrane

predominantly expressed in hemopoietic cells such as NK cells, subset of T-cells & monocytes
detected in leukocytes, spleen, & thymus
induced by T-cell receptor (TCR) ligation, which leads to enhanced NKG2D-HCST cell surface expression
down-regulated by IL21 in T-cells & NK cells
silencing of HCST suppresses cytolytic activity of T-cells & NK cells