Chromaffin cells express two 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 alpha-subunits (Mr approximately 130,000) bound IGF-I and IGF-II with identical affinity (Kd approximately 1 nM) and insulin with about 1000 times lower affinity. IGF-II receptors (Mr approximately 250,000) bound IGF-II with a Kd of 0.5 nM, IGF-I with about 10 times lower affinity and insulin with greater than 10,000 times lower affinity. The amounts of IGF-I and IGF-II receptors on the cell surface were 8 x 10(4) and 4 x 10(4) sites per cell, respectively. Insulin bound to a specific receptor with Kd approximately 2 nM and the amount of receptors was 1.5 x 10(4) sites per cell. IGF-I and IGF-II stimulated tyrosine kinase activity and autophosphorylation of the IGF-I receptor beta-subunit (Mr approximately 94,000) with equal potency (ED50 approximately 1 nM), whereas insulin was approximately 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.
Danielsen
A
A
Department of Clinical Chemistry, Bispebjerg Hospital, Copenhagen, Denmark.
Larsen
E
E
Gammeltoft
S
S
D000313:Adrenal Medulla / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D007700:Kinetics; D008970:Molecular Weight; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000302:isolation & purification / Q000378:metabolism*; D017451:Receptors, Somatomedin; D011994:Recombinant Proteins / Q000378:metabolism; D013002:Somatomedins / Q000378:metabolism*
D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D011994:Recombinant Proteins; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin