den Hertog J, Sap J, Pals C E, Schlessinger J, Kruijer W
Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Utrecht.
Cell Growth Differ. 1995 Mar;6(3):303-7.
Receptor Protein-Tyrosine Phosphatase alpha (RPTP alpha) is a transmembrane protein with two cytoplasmic catalytic protein-tyrosine phosphatase (PTP) domains and a relatively short (123 amino acids) extracellular domain. Here we report that treatment of transfected cells that express RPTP alpha with the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate, a direct activator of protein kinase C, induced a rapid, transient increase in RPTP alpha activity due to a 2- to 3-fold increase in substrate affinity. A transient increase in RPTP alpha serine phosphorylation was concomitant with the enhanced activity. Tryptic phosphopeptide mapping of RPTP alpha demonstrated that phosphorylation of three tryptic peptides was enhanced in response to phorbol ester. In vitro dephosphorylation of RPTP alpha from phorbol ester-treated cells reduced RPTP alpha activity to prestimulation levels, indicating that enhanced serine phosphorylation directly accounted for the increase in activity. Our results demonstrate that serine phosphorylation may play a key role in the regulation of the activity of transmembrane PTPs.
受体蛋白酪氨酸磷酸酶α（RPTPα）是一种跨膜蛋白，具有两个胞质催化蛋白酪氨酸磷酸酶（PTP）结构域和一个相对较短（123个氨基酸）的胞外结构域。在此我们报告，用佛波酯12-O-十四烷酰佛波醇-13-乙酸酯（蛋白激酶C的直接激活剂）处理表达RPTPα的转染细胞，由于底物亲和力增加2至3倍，导致RPTPα活性迅速、短暂升高。RPTPα丝氨酸磷酸化的短暂增加与活性增强同时出现。RPTPα的胰蛋白酶磷酸肽图谱显示，响应佛波酯，三个胰蛋白酶肽的磷酸化增强。对经佛波酯处理的细胞中的RPTPα进行体外去磷酸化，可使RPTPα活性降至刺激前水平，表明丝氨酸磷酸化增强直接导致了活性增加。我们的结果表明，丝氨酸磷酸化可能在跨膜PTP活性调节中起关键作用。
