Sahyoun N, McDonald O B, Farrell F, Lapetina E G
Wellcome Research Laboratories, Research Triangle Park, NC 27709.
Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2643-7. doi: 10.1073/pnas.88.7.2643.
A neuron-specific Ca2+/calmodulin-dependent protein kinase, CaM kinase Gr, phosphorylates selectively a Ras-related GTP-binding protein (Rap-1b) that is enriched in brain tissue. The phosphorylation reaction achieves a stoichiometry of about 1 and involves a serine residue near the carboxyl terminus of the substrate. Both CaM kinase Gr and cAMP-dependent protein kinase, but not CaM kinase II, phosphorylate identical or contiguous serine residues in Rap-1b. The rate of phosphorylation of Rap-1b by CaM kinase Gr is enhanced following autophosphorylation of the protein kinase. Other low molecular weight GTP-binding proteins belonging to the Ras superfamily, including Rab-3A, Rap-2b, and c-Ha-ras p21, are not phosphorylated by CaM kinase Gr. The phosphorylation of Rap-1b itself can be reversed by an endogenous brain phosphoprotein phosphatase. These observations provide a potential connection between a neuronal Ca2(+)-signaling pathway and a specific low molecular weight GTP-binding protein that may regulate neuronal transmembrane signaling, vesicle transport, or neurotransmitter release.
一种神经元特异性钙/钙调蛋白依赖性蛋白激酶，即钙调蛋白激酶Gr，可选择性地磷酸化一种在脑组织中含量丰富的Ras相关GTP结合蛋白（Rap-1b）。磷酸化反应的化学计量比约为1，且涉及底物羧基末端附近的一个丝氨酸残基。钙调蛋白激酶Gr和环磷酸腺苷依赖性蛋白激酶均可磷酸化Rap-1b中相同或相邻的丝氨酸残基，而钙调蛋白激酶II则不能。钙调蛋白激酶Gr自磷酸化后，其对Rap-1b的磷酸化速率会提高。属于Ras超家族的其他低分子量GTP结合蛋白，包括Rab-3A、Rap-2b和c-Ha-ras p21，均不能被钙调蛋白激酶Gr磷酸化。Rap-1b自身的磷酸化可被一种内源性脑磷蛋白磷酸酶逆转。这些观察结果揭示了神经元钙信号通路与一种特定的低分子量GTP结合蛋白之间的潜在联系，该蛋白可能参与调节神经元跨膜信号传导、囊泡运输或神经递质释放。
