DaSilva L, Howard O M, Rui H, Kirken R A, Farrar W L
Biological Carcinogenesis and Development Program, Program Resources Inc./DynCorp, Frederick, Maryland.
J Biol Chem. 1994 Jul 15;269(28):18267-70.
Prolactin (PRL) has recently been demonstrated to induce tyrosine phosphorylation and activation of the cytoplasmic tyrosine kinase JAK2 in PRL-dependent Nb2 lymphoma cells. The present study represents an initial effort to identify cytoplasmic regions of the PRL receptor (PRLR) that are critical to growth signal generation and JAK2 activation. Variably truncated rat PRLRs were stably expressed in the murine 32D cell line. PRL-induced proliferation was mediated by the full-length receptor and the mutant G328, which contains the membrane-proximal Homology Boxes 1 and 2 characteristic of hematopoietin receptors. In contrast, mutant receptors lacking either Box 2 or both Boxes 1 and 2 were not capable of transmitting a growth signal. The mitogenic capacity of the PRLR variants correlated with JAK2 association and activation, as well as with induction of mRNA levels for the growth-related gene ornithine decarboxylase. We conclude that mitogenic competence of rat PRLRs resides within the first 94 amino acids of the cytoplasmic domain. The data suggest that Homology Box 1/Box 2 region is critical to JAK2 phosphorylation and association with the PRLR. These findings will serve as a basis for more detailed molecular characterization of PRLR domains essential for JAK2 interaction and growth signal generation.
最近有研究表明，催乳素（PRL）可诱导PRL依赖的Nb2淋巴瘤细胞中细胞质酪氨酸激酶JAK2的酪氨酸磷酸化并激活该激酶。本研究旨在初步确定催乳素受体（PRLR）的细胞质区域，这些区域对于生长信号的产生和JAK2的激活至关重要。将不同程度截短的大鼠PRLR在小鼠32D细胞系中稳定表达。PRL诱导的增殖由全长受体和突变体G328介导，突变体G328包含造血因子受体特有的膜近端同源框1和2。相比之下，缺少框2或同时缺少框1和框2的突变受体无法传递生长信号。PRLR变体的促有丝分裂能力与JAK2的结合和激活以及与生长相关基因鸟氨酸脱羧酶的mRNA水平的诱导相关。我们得出结论，大鼠PRLR的促有丝分裂能力存在于细胞质结构域的前94个氨基酸内。数据表明同源框1/框2区域对于JAK2磷酸化以及与PRLR的结合至关重要。这些发现将为更详细地分子表征对JAK2相互作用和生长信号产生至关重要的PRLR结构域奠定基础。
