Kazlauskas A, Feng G S, Pawson T, Valius M
National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):6939-43. doi: 10.1073/pnas.90.15.6939.
Ligand-stimulated autophosphorylation of the platelet-derived growth factor receptor (PDGFR) beta subunit creates a number of binding sites for SH2-containing proteins. One of the PDGFR-associated proteins is a 64-kDa protein of unknown identity and function. We present data indicating that the 64-kDa protein that associates with the activated PDGFR is Syp (also called SH-PTP2, PTP-1D, or SH-PTP3), the ubiquitously expressed 64-kDa SH2-containing protein-tyrosine phosphatase. Phosphorylation of Tyr-1009 in the C terminus of the PDGFR is required for the stable association of Syp, suggesting that phosphorylation of this residue creates a binding site for the Syp SH2 domains. Although Syp stably associates with the PDGFR, this event is not required for PDGF-stimulated tyrosine phosphorylation of Syp. These data raise the interesting possibility that protein-tyrosine phosphatases contribute to the intracellular relay of biological signals originating from receptor tyrosine kinases such as the PDGFR.
配体刺激的血小板衍生生长因子受体（PDGFR）β亚基的自磷酸化产生了许多含SH2结构域蛋白的结合位点。一种与PDGFR相关的蛋白是一种身份和功能未知的64 kDa蛋白。我们提供的数据表明，与活化的PDGFR相关的64 kDa蛋白是Syp（也称为SH-PTP2、PTP-1D或SH-PTP3），即普遍表达的含64 kDa SH2结构域的蛋白酪氨酸磷酸酶。Syp的稳定结合需要PDGFR C末端的Tyr-1009磷酸化，这表明该残基的磷酸化产生了一个Syp SH2结构域的结合位点。尽管Syp与PDGFR稳定结合，但这一事件并非PDGF刺激Syp酪氨酸磷酸化所必需。这些数据提出了一个有趣的可能性，即蛋白酪氨酸磷酸酶参与了源自受体酪氨酸激酶（如PDGFR）的生物信号的细胞内传递。
