Hematopoietic cell signal transducer (HCST)

Hematopoietic cell signal transducer (HCST), also known as DAP10, is a transmembrane adaptor protein encoded by the HCST gene and primarily expressed in lymphoid and myeloid cells. It serves as an integral accessory component of the immune recognition receptor complex, especially with the C-type lectin-like receptor NKG2D (KLRK1). HCST contains a cytoplasmic YxxM motif, which is critical for recruitment of phosphatidylinositol 3-kinase (PI3K) and downstream signaling events such as calcium mobilization and activation of MAPK and STAT pathways. The KLRK1-HCST complex is essential for NK cell-mediated cytotoxicity against stressed cells, including those undergoing viral infection or tumor transformation; it also provides costimulation for TCR signals in T cells and supports cytokine production. HCST’s expression and activity are dynamically regulated by cytokines, and its dysregulation is linked to defective immunosurveillance and poor prognosis in cancers such as clear cell renal cell carcinoma. HCST is not a classic drug target itself, but it is a central signaling node controlling immune cell effector functions, survival, and cell adhesion.

Other names

DAP10KAP10PIK3APDNAX-activation protein 10Membrane protein DAP10Transmembrane adapter protein KAP10kinase-associated protein of ~10 kDaphosphoinositide-3-kinase adaptor proteinUNQ587/PRO1157DKFZP586C1522

Drugs targeting HCST would likely act by modulating immune cell activation (primarily NK cell cytotoxicity and T cell costimulation) via inhibition or stimulation of the KLRK1-HCST complex or its downstream PI3K, MAP2K/ERK, and JAK2/STAT5 signaling pathways