Division of Inflammation Biology, La Jolla Institute of Allergy and Immunology, La Jolla, CA 92037, USA.
Sci Signal. 2013 May 28;6(277):pe20. doi: 10.1126/scisignal.2004290.
An early step in tumor metastasis is a reduction in cell-cell adhesion to enable cell scattering. Contacts between cells are stabilized by accumulation in the plasma membrane of the small guanosine triphosphatase (GTPase) Rap1B. The membrane localization of Rap1B is increased when it is posttranslationally modified by prenylation of its C-terminal Cys-Ala-Ala-X motif. A new study shows that Rap1B prenylation and plasma membrane localization were reduced when Rap1B was phosphorylated by protein kinase A (PKA). In some tumors, high adenosine production and an abundance of G(s)-coupled adenosine A(2B) receptors would be expected to cause persistent PKA signaling and reduced Rap1B prenylation. These findings suggest that adenosine signaling reduces prenylation and plasma membrane localization of Rap1B, resulting in enhanced tumor cell scattering and invasiveness.
肿瘤转移的早期步骤是减少细胞间的粘附，从而使细胞分散。细胞间的接触通过小 GTP 酶（GTPase）Rap1B 在质膜中的积累而稳定下来。当 Rap1B 的 C 末端半胱氨酸-丙氨酸-丙氨酸-X 基序发生异戊二烯基化的翻译后修饰时，Rap1B 的膜定位增加。一项新的研究表明，当 Rap1B 被蛋白激酶 A（PKA）磷酸化时，Rap1B 的异戊烯基化和质膜定位减少。在一些肿瘤中，高腺苷的产生和丰富的 G(s)-偶联腺苷 A(2B)受体预计会导致持续的 PKA 信号和 Rap1B 异戊烯基化的减少。这些发现表明，腺苷信号降低了 Rap1B 的异戊烯基化和质膜定位，导致肿瘤细胞散射和侵袭性增强。
