HCST
Description
The HCST (hematopoietic cell signal transducer) is a protein-coding gene located on chromosome 19.
HCST may refer to: Hematopoietic cell signal transducer also know as DNAX-activation protein 10, Membrane protein DAP10, Transmembrane adapter protein KAP10.
HCST, also known as DAP10, is a transmembrane adapter protein that associates with KLRK1 to form an activation receptor complex (KLRK1-HCST) on lymphoid and myeloid cells. This complex plays a critical role in triggering cytotoxicity against target cells, particularly those expressing stress-induced ligands like MICA, MICB, and ULBPs. These ligands are upregulated in response to viral infection and tumor transformation. HCST acts as a docking site for PI3-kinase PIK3R1 and GRB2, key signaling molecules. Upon interaction with ULBPs, KLRK1-HCST activates calcium mobilization and downstream signaling pathways involving PIK3R1, MAP2K/ERK, and JAK2/STAT5. PIK3R1 and GRB2 are essential for full KLRK1-HCST-mediated activation and subsequent killing of target cells. In NK cells, KLRK1-HCST signaling directly induces cytotoxicity and enhances cytokine production, while in T-cells, it serves as a costimulator for TCR-induced signals. KLRK1-HCST receptor is crucial for immune surveillance against tumors and is required for the killing of tumor cells. Melanoma cells lacking KLRK1 ligands escape NK cell-mediated immune surveillance.
HCST is also known as DAP10, KAP10, PIK3AP.
Associated Diseases
- melorheostosis
- Gorham-Stout disease
- 12q14 microdeletion syndrome
- dacryocystitis-osteopoikilosis syndrome
- pyknoachondrogenesis
- autosomal recessive osteopetrosis 6
- osteomesopyknosis
- severe combined immunodeficiency due to CTPS1 deficiency
- osteosclerosis-ichthyosis-premature ovarian failure syndrome
- immunodeficiency 18
- gnathodiaphyseal dysplasia
- Wiskott-Aldrich syndrome
- hyperostosis corticalis generalisata
- autosomal dominant osteosclerosis, Worth type
- melorheostosis with osteopoikilosis
- autosomal recessive hypophosphatemic rickets
- dentin dysplasia-sclerotic bones syndrome