Somatostatin receptor type 2 (SSTR2)

Somatostatin receptor type 2 (SSTR2), encoded by the SSTR2 gene on chromosome 17q25.1, is a G-protein coupled receptor for somatostatin-14 and somatostatin-28 peptides. It is highly expressed in the pancreas, cerebrum, and kidney and is a 369 amino acid protein. SSTR2 primarily exists as the SSTR2A variant in humans. It mediates diverse physiological functions including inhibition of hormone secretion, neurological effects, anti-proliferative actions, anti-angiogenesis, and regulation of intracellular signaling pathways like adenylyl cyclase, PTP, PLC, and calcium channels. SSTR2 is a significant therapeutic target, particularly due to its overexpression in various tumors, especially neuroendocrine tumors, where its expression is linked to improved prognosis. It is exploited for diagnostic imaging and therapy (PRRT) and is a target for somatostatin analogs used in conditions like acromegaly and neuroendocrine tumors. The receptor is also being investigated for potential applications in diabetic complications, inflammatory conditions, pain, and meningiomas. It can form homo- and heterodimers with other somatostatin receptor subtypes, influencing its function.

SSTR2 is a G-protein coupled receptor that mediates its effects primarily by inhibiting adenylyl cyclase via pertussis toxin-sensitive G proteins. It also stimulates phosphotyrosine phosphatase and PLC through both pertussis toxin-sensitive and -insensitive G proteins, inhibits voltage-dependent calcium channels, and negatively regulates insulin receptor signaling via PTPN6. Activation leads to inhibition of hormone secretion, antiproliferative effects (via MAPK/CDKN1B), anti-angiogenesis, and stimulation of apoptosis.