CHROMAFFIN CELLS EXPRESS 2 TYPES OF INSULIN-LIKE GROWTH-FACTOR RECEPTORS

The receptor binding, internalization and tyrosine kinase activation of insulin-like growth factors, IGF-I and IGF-II have been investigated in cultured adult bovine chromaffin cells. IGF-I receptor α-subunits (Mr ∼130,000) bound IGF-I and IGF-II with identical affinity (Kd ∼1 nM) and insulin with about 1000 times lower affinity. IGF-II receptors (Mr ∼250,000) bound IGF-II with a Kd of 0.5 nM, IGF-I with about 10 times lower affinity and insulin with >10,000 times lower affinity. The amounts of IGF-I and IGF-II receptors on the cell surface were 8 × 104 and 4 × 104 sites per cell, respectively. Insulin bound to a specific receptor with Kd ∼2 nM and the amount of receptors was 1.5 × 104 sites per cell. IGF-I and IGF-II stimulated tyrosine kinase activity and autophosphorylation of the IGF-I receptor ß-subunit (Mr ∼94,000) with equal potency (ED50 ∼1 nM), whereas insulin was ∼5 times less potent. Both IGF-I and IGF-II were internalized after their binding to cell surface receptors. Mannose-6-phosphate, which binds to the IGF-II receptor, did not alter the binding or internalization of IGF-II. It is concluded that IGF-I and IGF-II can exert their biological effects in chromaffin cells by activation of the IGF-I receptor tyrosine kinase or by interaction with the IGF-II receptor. © 1990.