Ectoprotein kinase in the regulation of cellular responsiveness to extracellular ATP.
Ectoprotein kinase in the regulation of cellular responsiveness to extracellular ATP.
复制标题
胞外蛋白激酶调节细胞对细胞外 ATP 的反应。
DOI：
10.1111/j.1749-6632.1990.tb37689.x
复制
发表时间：
1990
影响因子：
5.2
通讯作者：
Kornecki,E
中科院分区：
文献类型：
--
作者：
Ehrlich,YH;Hogan,MV;Pawlowska,Z;Naik,U;Kornecki,E
细胞内蛋白质的可逆磷酸化已被确立为许多细胞功能的关键调节机制。在这个过程中，蛋白激酶转移ATP的γ-磷酸盐，与特定的蛋白质形成共价键。另一条研究路线已经证明，细胞外ATP是各种细胞系统中的有效生理调节剂。虽然细胞外ATP的许多生理效应被证明是由嘌呤能受体的作用介导的，但细胞外蛋白磷酸化系统也可能涉及细胞对细胞外ATP的反应性的机制。在各种细胞表面的胞外蛋白激酶的鉴定为这种机制的存在提供了证据，并揭示了蛋白磷酸化系统的调节能力如何延伸到细胞外环境。细胞外蛋白磷酸化活性在调节细胞功能中可能发挥的多功能作用通过在细胞表面存在用于该活性的多种蛋白质底物来强调。每种这样的表面磷蛋白可能具有独特的功能。图5描绘了由胞吐分泌的细胞外ATP与这些分泌神经元的特定生理功能之间的假设关系。基于本文所述的研究结果，我们提出细胞外ATP可以被两种类型的细胞外蛋白激酶利用：膜结合的胞外蛋白激酶和可溶性胞外蛋白激酶。外蛋白激酶可以由外激酶从细胞表面脱离而产生，或者是通过胞吐作用从刺激的细胞与ATP共释放的囊内蛋白。分泌细胞表面特定蛋白质的磷酸化可能对其自身的突触前活动具有重要的反馈控制。胞外蛋白激酶可以通过磷酸化参与分泌的离子通道和/或磷酸化转运蛋白来发挥这种反馈调节作用，所述转运蛋白对释放的递质分子进行再摄取。受体的磷酸化可以调节细胞间通讯，整合素的磷酸化可以调节细胞表面与细胞外基质组分的相互作用。尽管图5中提出的大多数关系仍然是假设的，但应该可以通过产生针对特定表面磷蛋白磷酸化位点的抗体，以直接的方式在实验上对其进行测试。这种抗体抑制蛋白质磷酸化而不穿透细胞的能力提供了用于直接测试各种细胞中的外蛋白激酶和外蛋白激酶活性的潜在生理功能的实验范例。
The reversible phosphorylation of intracellular proteins has been established as a key regulatory mechanism in numerous cellular functions. In this process the enzyme protein kinase transfers the gamma-phosphate of ATP to form a covalent bond with specific proteins. Another line of investigation has demonstrated that extracellular ATP is a potent physiological regulator in various cellular systems. Although many of the physiological effects of extracellular ATP were shown to be mediated by the action of purinergic receptors, it is possible that extracellular protein phosphorylation systems are also implicated in the mechanisms underlying the responsiveness of cells to extracellular ATP. The identification of ectoprotein kinase at the surface of various cells has provided evidence for the existence of such mechanisms, and revealed how the regulatory powers of protein phosphorylation systems can extend to the extracellular environment. The versatile roles that extracellular protein phosphorylation activity may play in the regulation of cellular functions is underscored by the presence of multiple protein substrates for this activity at the cell surface. Each such surface phosphoprotein may have a unique function. FIGURE 5 depicts the hypothetical relationships between the extracellular ATP secreted by exocytosis and the specific physiological function of these secreting neurons. Based on findings described in this article, we propose that extracellular ATP can be utilized by two types of extracellular protein kinase: a membrane-bound ectoprotein kinase, and a soluble exoprotein kinase. The exoprotein kinase can originate by detachment of an ectokinase from the cell surface, or be an intravesicular protein that is coreleased with ATP by exocytosis from stimulated cells. Phosphorylation of specific proteins at the surface of a secreting cell may have an important feedback control over its own presynaptic activity. The ectoprotein kinase could exert this feedback regulation by phosphorylating ion channels involved in secretion, and/or by phosphorylating transporters that carry out the reuptake of released transmitter molecules. Phosphorylation of receptors can regulate intercellular communication, and phosphorylation of integrins could regulate the interaction of the cell surface with components of the extracellular matrix. Although most of the relationships suggested in FIGURE 5 are still hypothetical, it should be possible to test them experimentally in a direct manner by raising antibodies against the phosphorylated sites of specific surface phosphoproteins. The ability of such antibodies to inhibit protein phosphorylation without penetrating the cells provides an experimental paradigm for the direct testing of potential physiological function of ecto-and exoprotein kinase activities in a variety of cells.