Lesley J, Hyman R, Kincade P W
Department of Cancer Biology, Salk Institute, San Diego, California 92186.
Adv Immunol. 1993;54:271-335. doi: 10.1016/s0065-2776(08)60537-4.
It is now generally accepted that CD44 is a cell adhesion receptor and that hyaluronan is one of its ligands. Like many cell adhesion receptors, CD44 is broadly distributed, and its ligand, hyaluronan, is a common component of extracellular matrices and extracellular fluids. Yet a great variety of responses has been reported to result from CD44 ligation. These include cell adhesion, cell migration, induction (or at least support) of hematopoietic differentiation, effects on other cell adhesion mechanisms, and interaction with cell activation signals. This diversity of responses indicates that downstream events following ligand binding by CD44 may vary depending on the cell type expressing CD44 and on the environment of that cell. CD44 is expressed on cells in the early stages of hematopoiesis and has been shown to participate in at least some aspects of the hematopoietic process. In mature lymphocytes, CD44 is upregulated in response to antigenic stimuli and may participate in the effector stage of immunological responses. Along with other adhesion receptors that show alterations in expression after activation, CD44 probably contributes to differences in the recirculation patterns of different lymphocyte subpopulations. CD44 ligand-binding function on lymphocytes is strictly regulated, such that most CD44-expressing cells do not constitutively bind ligand. Ligand-binding function may be activated as a result of differentiation, inside-out signaling, and/or extracellular stimuli. This regulation, which in some situations can be rapid and transient, potentially provides exquisite specificity to what would otherwise be a common interaction. CD44 is not a single molecule, but a diverse family of molecules generated by alternate splicing of multiple exons of a single gene and by different posttranslational modifications in different cell types. It is not yet clear how these modifications influence ligand-binding function. The significance of the multiple isoforms of CD44 is not understood, but association of some isoforms with malignancies has been observed. And in at least some experimental systems, a contribution of CD44 isoforms to metastatic behavior has been demonstrated.
现在人们普遍认为，CD44是一种细胞粘附受体，透明质酸是其配体之一。与许多细胞粘附受体一样，CD44分布广泛，其配体透明质酸是细胞外基质和细胞外液的常见成分。然而，据报道，CD44的连接会导致各种各样的反应。这些反应包括细胞粘附、细胞迁移、造血分化的诱导（或至少是支持）、对其他细胞粘附机制的影响以及与细胞激活信号的相互作用。这种反应的多样性表明，CD44与配体结合后的下游事件可能因表达CD44的细胞类型及其所处环境而异。CD44在造血早期阶段的细胞上表达，并已被证明参与造血过程的至少某些方面。在成熟淋巴细胞中，CD44会因抗原刺激而上调，并可能参与免疫反应的效应阶段。与其他在激活后表达会发生改变的粘附受体一起，CD44可能导致不同淋巴细胞亚群再循环模式的差异。淋巴细胞上CD44的配体结合功能受到严格调控，以至于大多数表达CD44的细胞不会组成性地结合配体。配体结合功能可能会因分化、由内向外信号传导和/或细胞外刺激而被激活。这种调控在某些情况下可能是快速且短暂的，它可能为原本普通的相互作用提供精确的特异性。CD44不是单个分子，而是一个由单个基因的多个外显子的可变剪接以及不同细胞类型中不同的翻译后修饰产生的多样化分子家族。目前尚不清楚这些修饰如何影响配体结合功能。CD44多种异构体的意义尚不清楚，但已观察到某些异构体与恶性肿瘤有关。并且在至少一些实验系统中，已证明CD44异构体对转移行为有影响。
