Nakano N, Nakao A, Ishidoh K, Tsuboi R, Kominami E, Okumura K, Ogawa H
Atopy (Allergy) Research Center, Juntendo University School of Medicine, Tokyo, Japan.
Br J Dermatol. 2005 Jul;153(1):37-45. doi: 10.1111/j.1365-2133.2005.06583.x.
CDK5 is a member of proline-directed serine/threonine kinases. Although its cDNA was originally cloned as a homologue to those for the other members of the cyclin-dependent kinase (CDK) family, CDK5 has been shown to function differently from other CDKs. CDK5 is activated by non-cyclin partners, p35 and p39, and important during brain development by influencing adhesion, migration and differentiation of neurones.
We sought to investigate the expression and functions of CDK5 in human keratinocytes.
Expression of CDK5/p35, interaction of CDK5/p35 with adhesion molecules, and its roles in cell-cell and cell-matrix adhesion were studied by reverse transcriptase-polymerase chain reaction, immunoblotting and aggregation/adhesion assays in primary cultured normal human keratinocytes from infant foreskins and a human keratinocyte HaCaT cell line. Localization of CDK5 and p35 in normal human epidermis and psoriatic epidermis was studied by immunohistochemistry.
Both CDK5 and p35 were expressed in primary cultured keratinocytes, HaCaT cells and normal human epidermis. Roscovitine, an inhibitor of CDK5, enhanced Ca2+-dependent (cadherin-dependent) aggregation of HaCaT cells whereas it inhibited adhesion of HaCaT cells to fibronectin associated with reduced active states of beta1 integrin. Interestingly, psoriatic skin showed reduced CDK5 and p35 expression in the lower half of the epidermis, which might be associated with decreased amount of activated beta1 integrin in the epidermis of psoriatic skin.
CDK5/p35 may be involved in cell-cell and cell-matrix adhesion in human keratinocytes by differently regulating cadherins and integrins. Furthermore, reduced expression of CDK5/p35 in the epidermis might be involved in the pathogenesis of psoriasis.
细胞周期蛋白依赖性激酶5（CDK5）是脯氨酸定向丝氨酸/苏氨酸激酶家族的成员。尽管其cDNA最初作为细胞周期蛋白依赖性激酶（CDK）家族其他成员的同源物被克隆，但CDK5已被证明其功能与其他CDK不同。CDK5由非细胞周期蛋白伴侣p35和p39激活，在脑发育过程中通过影响神经元的黏附、迁移和分化发挥重要作用。
我们试图研究CDK5在人角质形成细胞中的表达和功能。
通过逆转录聚合酶链反应、免疫印迹以及聚集/黏附试验，在来自婴儿包皮的原代培养正常人角质形成细胞和人角质形成细胞HaCaT细胞系中，研究CDK5/p35的表达、CDK5/p35与黏附分子的相互作用及其在细胞-细胞和细胞-基质黏附中的作用。通过免疫组织化学研究CDK5和p35在正常人表皮和银屑病表皮中的定位。
CDK5和p35在原代培养的角质形成细胞、HaCaT细胞和正常人表皮中均有表达。CDK5抑制剂roscovitine增强了HaCaT细胞的Ca2+依赖性（钙黏蛋白依赖性）聚集，而抑制了HaCaT细胞与纤连蛋白的黏附，同时β1整合素的活性状态降低。有趣的是，银屑病皮肤表皮下半部分的CDK5和p35表达降低，这可能与银屑病皮肤表皮中活化的β1整合素数量减少有关。
CDK5/p35可能通过不同地调节钙黏蛋白和整合素参与人角质形成细胞的细胞-细胞和细胞-基质黏附。此外，表皮中CDK5/p35表达降低可能参与银屑病的发病机制。
