Puré E, Camp R L, Peritt D, Panettieri R A, Lazaar A L, Nayak S
Wistar Institute, Philadelphia, Pennsylvania 19104-4268.
J Exp Med. 1995 Jan 1;181(1):55-62. doi: 10.1084/jem.181.1.55.
CD44 is a cell surface adhesion molecule that plays a role in leukocyte extravasation, leukopoiesis, T lymphocyte activation, and tumor metastasis. The principal known ligand for CD44 is the glycosaminoglycan hyaluronate, (HA), a major constituent of extracellular matrices. CD44 expression is required but is not sufficient to confer cellular adhesion to HA, suggesting that the adhesion function of the receptor is regulated. We recently demonstrated that CD44 in primary leukocytes is phosphorylated in a cell type- and activation state-dependent fashion. In this study we demonstrate that serines 325 and 327 within the cytoplasmic domain of CD44 are required for the constitutive phosphorylation of CD44 in T cells. Furthermore, we demonstrate that cells expressing mutated CD44 containing a serine to glycine substitution at position 325 or a serine to alanine substitution at amino acid 327 are defective in HA binding, CD44-mediated adhesion of T cells to smooth muscle cells, as well as ligand-induced receptor modulation. The effect of these mutations can be partially reversed by a monoclonal anti-CD44 antibody that enhances CD44-mediated HA binding.
CD44是一种细胞表面黏附分子，在白细胞外渗、白细胞生成、T淋巴细胞活化及肿瘤转移中发挥作用。已知CD44的主要配体是糖胺聚糖透明质酸（HA），它是细胞外基质的主要成分。CD44的表达是细胞黏附HA所必需的，但并不足以赋予细胞与HA的黏附能力，这表明该受体的黏附功能受到调控。我们最近证实，原代白细胞中的CD44以细胞类型和激活状态依赖的方式发生磷酸化。在本研究中，我们证明CD44胞质结构域内的丝氨酸325和327是T细胞中CD44组成型磷酸化所必需的。此外，我们还证明，表达在第325位丝氨酸突变为甘氨酸或第327位氨基酸丝氨酸突变为丙氨酸的突变型CD44的细胞，在HA结合、CD44介导的T细胞与平滑肌细胞黏附以及配体诱导的受体调节方面存在缺陷。这些突变的影响可被一种增强CD44介导的HA结合的单克隆抗CD44抗体部分逆转。
