Sahin M, Hockfield S
Section of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06510.
J Neurosci. 1993 Nov;13(11):4968-78. doi: 10.1523/JNEUROSCI.13-11-04968.1993.
Previous studies of the developing nervous system have shown that cell-cell and cell-matrix interactions are involved in a variety of processes such as the proliferation, migration, and differentiation of neurons. While many cell-surface molecules have been identified, the signal transduction mechanisms through which they modify cellular responses are poorly understood. Recent studies have described a new and large family of enzymes, protein tyrosine phosphatases (PTPases), that may play a key role in transduction of cell surface events. Opposing the actions of protein tyrosine kinases (PTKs), PTPases can determine the state of tyrosine phosphorylation of a protein and regulate its function. Within the family of PTPases, two subgroups have been characterized: low-molecular-weight cytoplasmic (nonreceptor) PTPases and high-molecular-weight transmembrane (receptor) PTPases. Many receptor PTPases have fibronectin type III and/or Ig-like domains in their extracellular domains, suggesting that they have dual functions: cell adhesion and signal transduction. Such molecules may play a role in cellular recognition events that mediate the accurate assembly of the nervous system. Using polymerase chain reaction with degenerate primers and a neonatal rat cortex cDNA library, we have identified a number of putative PTPase domains expressed in brain. Three are characterized here. These three sequences are most abundantly expressed in the developing cortex and so are named cortex-enriched protein tyrosine phosphatases (CPTPs) 1, 2, and 3. CPTP1 and CPTP3 show sequence homology to receptor PTPases and detect multiple high-molecular-weight mRNAs that are expressed preferentially in the developing CNS. Analysis of a longer cDNA indicates that CPTP1 and CPTP3 are the first and second phosphatase domains of a single receptor PTPase. CPTP2 identifies a single, smaller mRNA species with sequence homology to nonreceptor PTPases. Within the CNS, mRNAs detected by all three CPTPs are expressed at highest levels during prenatal and early postnatal days and are downregulated in the adult. In situ hybridization demonstrates that the CPTPs are expressed by progenitor cells and developing neurons. The spatial and temporal regulation of CPTPs suggests that they may play a role in neuronal development.
以往对发育中的神经系统的研究表明，细胞间和细胞与基质间的相互作用参与了多种过程，如神经元的增殖、迁移和分化。虽然已经鉴定出许多细胞表面分子，但对它们调节细胞反应的信号转导机制却知之甚少。最近的研究描述了一个新的、庞大的酶家族——蛋白酪氨酸磷酸酶（PTPases），它们可能在细胞表面事件的转导中起关键作用。与蛋白酪氨酸激酶（PTKs）的作用相反，PTPases可以决定蛋白质酪氨酸磷酸化的状态并调节其功能。在PTPases家族中，已鉴定出两个亚组：低分子量细胞质（非受体）PTPases和高分子量跨膜（受体）PTPases。许多受体PTPases在其细胞外结构域中具有纤连蛋白III型和/或免疫球蛋白样结构域，这表明它们具有双重功能：细胞黏附和信号转导。这类分子可能在介导神经系统精确组装的细胞识别事件中发挥作用。利用简并引物聚合酶链反应和新生大鼠皮质cDNA文库，我们鉴定出了一些在脑中表达的假定PTPase结构域。这里对其中三个进行了表征。这三个序列在发育中的皮质中表达最为丰富，因此被命名为皮质富集蛋白酪氨酸磷酸酶（CPTPs）1、2和3。CPTP1和CPTP3与受体PTPases具有序列同源性，并检测到多个在发育中的中枢神经系统中优先表达的高分子量mRNA。对一个更长的cDNA的分析表明，CPTP1和CPTP3是单个受体PTPase的第一和第二磷酸酶结构域。CPTP2鉴定出一个与非受体PTPases具有序列同源性的单一、较小的mRNA种类。在中枢神经系统中，所有三种CPTPs检测到的mRNA在产前和出生后早期表达水平最高，在成体中表达下调。原位杂交表明，CPTPs由祖细胞和发育中的神经元表达。CPTPs的时空调节表明它们可能在神经元发育中发挥作用。
