Vaillancourt R R, Gardner A M, Kazlauskas A, Johnson G L
Division of Basic Sciences, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206, USA.
Oncogene. 1996 Jul 4;13(1):151-9.
The PDGF beta-receptor in which the active-site lysine in the kinase domain has been mutated to arginine (K634R) tacks intrinsic kinase activity. When expressed in HepG2 cells, the kinase-inactive PDGF beta-receptor was tyrosine phosphorylated in response to PDGF-BB. Previously, HepG2 cells were thought to be devoid of PDGF alpha-receptor primarily due to lack of specific antibody which precluded detection of the PDGF alpha-receptor. In fact, these cells express low levels of PDGF alpha-receptor. In HepG2 cells that express the kinase-inactive PDGF beta-receptor, PDGF-BB activates the PDGF alpha-receptors to trans phosphorylate the kinase-inactive PDGF beta-receptor in an intermolecular fashion. As a result, stimulation of HepG2 cells that express the kinase-inactive receptor leads to activation of serine/threonine kinases of the MAP kinase cascade which include RAF-1, MEK-1 and p42 MAP kinase. In contrast, the kinase-inactive receptor does not activate any signaling pathways when it is expressed in PC12 cells which do not express the endogenous PDGF alpha-receptor. Thus, the kinase-inactive K634R PDGF beta-receptor is able to enhance PDGF-BB signaling in HepG2 cells that express the PDGF alpha-receptor.
激酶结构域中的活性位点赖氨酸已突变为精氨酸（K634R）的血小板衍生生长因子β受体（PDGFβ受体）缺乏内在激酶活性。当在HepG2细胞中表达时，无激酶活性的PDGFβ受体在血小板衍生生长因子BB（PDGF-BB）的作用下发生酪氨酸磷酸化。以前，HepG2细胞被认为主要由于缺乏可检测PDGFα受体的特异性抗体而没有PDGFα受体。实际上，这些细胞表达低水平的PDGFα受体。在表达无激酶活性的PDGFβ受体的HepG2细胞中，PDGF-BB激活PDGFα受体，以分子间方式反式磷酸化无激酶活性的PDGFβ受体。结果，对表达无激酶活性受体的HepG2细胞的刺激导致丝裂原活化蛋白激酶（MAP激酶）级联反应的丝氨酸/苏氨酸激酶激活，其中包括RAF-1、MEK-1和p42 MAP激酶。相反，当无激酶活性的受体在不表达内源性PDGFα受体的PC12细胞中表达时，它不会激活任何信号通路。因此，无激酶活性的K634R PDGFβ受体能够增强在表达PDGFα受体的HepG2细胞中的PDGF-BB信号传导。
