Induction of two transformation-sensitive membrane polypeptides in normal rat kidney cells by iron deprivation.

Rapid depletion of iron from the growth medium induces the synthesis of two membrane proteins with a subunit molecular weight of 160,000 (160K) and 130,000 (130K) in cultured normal rat kidney cells. When iron is maintained at normal levels in the growth medium of normal rat kidney cells, the synthesis of the 160K and 130K proteins is suppressed. We found that 160K and 130K are the underglycosylated forms of two membrane glycoproteins, 163K and 132K, respectively. We estimated the apparent turnover rate of the underglycosylated proteins and showed that it is slower than that of the fully glycosylated forms. Upon removal of iron from the growth medium pf simian virus 40-transformed normal rat kidney cells and Kirsten sarcoma virus-transformed normal rat kidney cells, 160K and 130K did not increase to levels comparable to those of normal rat kidney cells. Two different clones of simian virus 40-transformed normal rat kidney cells subjected to iron deprivation showed greatly reduced levels of 160K, and in one of these clones, 130K was absent. Kirsten sarcoma virus-transformed normal rat kidney cells also showed a defective response to iron deprivation manifested by reduced levels of both 160K and 130K. Additional studies indicate that these glycoproteins are membrane-associated procollagen molecules. The alteration in the coordinated induction of 160K and 130K in transformed cells suggests that these membrane-associated proteins may have an important role in transformation.