Stasiak P C, Purkis P E, Leigh I M, Lane E B
Cell Structure Laboratory, Imperial Cancer Research Fund, Hertfordshire, U.K.
J Invest Dermatol. 1989 May;92(5):707-16. doi: 10.1111/1523-1747.ep12721500.
The type I keratin 19 is unusual in its tissue distribution in that under normal circumstances it does not seem to be restricted, as the other keratins are, to expression in either stratified or simple epithelia. In addition to the previously reported distribution of keratin 19 in human tissues, we have observed keratin 19 in epidermal basal cells, in a defined region of the hair follicle, and in nipple epidermis. We noticed that expression of keratin 19 appears to be especially characteristic of regions of labile or variable cellular differentiation as indicated by the presence of multiple keratin phenotypes in close proximity to each other. Using a monoclonal antibody recognizing keratin 19 (LP2K) to screen a human placenta cDNA expression library, we have isolated, cloned, and sequenced cDNA coding for full-length human keratin 19, as confirmed by its reactivity with several other known anti-keratin 19 monoclonal antibodies and by the near identity of its sequence with that of the bovine keratin 19 homologue. This similarity extends to both proteins being truncated at the C-terminal end to only 13 amino acids beyond the rod domain. Although the amino acid homology over the N-terminal and helical rod domains is particularly high, the human and bovine proteins diverge substantially over the short C-terminal domain, which suggests that this region has no conserved function. Comparison with other type I keratins indicates that the closest evolutionary neighbors of keratin 19 are keratinocyte keratins, probably 13 and 14, and not the simple epithelial keratin 18. Assessing the histochemistry and sequence data together, we propose that the cell may use this apparently deficient keratin as a "neutral" keratin. While unimpaired in its ability to polymerize (keeping the cell integrated into the epithelial sheet via filament-desmosome networks), keratin 19 expression does not irrevocably commit a cell to any one of the local differentiation options. Such predicted differentiational flexibility may also imply vulnerability to transformation.
I型角蛋白19在组织分布上与众不同，在正常情况下，它似乎不像其他角蛋白那样局限于在复层或单层上皮中表达。除了先前报道的角蛋白19在人体组织中的分布外，我们还在表皮基底细胞、毛囊的特定区域以及乳头表皮中观察到了角蛋白19。我们注意到，角蛋白19的表达似乎特别具有不稳定或可变细胞分化区域的特征，这表现为彼此紧邻的区域存在多种角蛋白表型。使用识别角蛋白19的单克隆抗体（LP2K）筛选人胎盘cDNA表达文库，我们分离、克隆并测序了编码全长人角蛋白19的cDNA，这通过它与其他几种已知的抗角蛋白19单克隆抗体的反应性以及其序列与牛角蛋白19同源物序列的近乎一致性得到证实。这种相似性延伸到两种蛋白质在C末端均被截短，仅在杆状结构域之后有13个氨基酸。尽管N末端和螺旋杆状结构域的氨基酸同源性特别高，但人和牛的蛋白质在短的C末端结构域上有很大差异，这表明该区域没有保守功能。与其他I型角蛋白比较表明，角蛋白19最接近的进化邻居是角质形成细胞角蛋白，可能是角蛋白13和14，而不是单层上皮角蛋白18。综合评估组织化学和序列数据，我们提出细胞可能将这种明显有缺陷的角蛋白用作“中性”角蛋白。虽然角蛋白19聚合的能力未受损（通过细丝 - 桥粒网络使细胞整合到上皮片中），但其表达不会不可逆转地使细胞定向于任何一种局部分化选择。这种预测的分化灵活性也可能意味着易发生转化。
