Dhj. Vanweering et al., EXPRESSION OF THE RECEPTOR TYROSINE KINASE RET ON THE PLASMA-MEMBRANEIS DEPENDENT ON CALCIUM, The Journal of biological chemistry, 273(20), 1998, pp. 12077-12081
Mutations in the Ret receptor tyrosine kinase are responsible for a va
riety of human syndromes, including multiple endocrine neoplasia 2 and
Hirschsprung's disease. Ret is expressed as a 180-kDa precursor form
in the endoplasmic reticulum and a 170-kDa mature form at the plasma m
embrane. Here we show that expression of p170(ret) is dependent on cal
cium. Depletion of extracellular calcium completely blocks p170(ret) e
xpression, which is not caused by a decrease in half-life of p170(ret)
at the plasma membrane but by a defect in processing of p150(ret) int
o p170(ret). This processing defect can be mimicked by treating the ce
lls with thapsigargin, a drug that releases calcium from internal stor
es, indicating that reduction in luminal calcium is responsible for th
e processing defect. We propose that a relatively high concentration o
f luminal calcium is necessary for the proper folding of Bet in the en
doplasmic reticulum.