MITOGENIC SIGNAL TRANSDUCTION IN BALB/MK KERATINOCYTES

BALB/MK 角质形成细胞中的有丝分裂信号转导

• 批准号: 3874781
• 负责人: S A AARONSON
• 金额: --
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3874781
• 关键词: biological signal transduction; cell growth regulation; enzyme induction /repression; epidermal growth factor; fibroblast growth factor; human tissue; insulinlike growth factor; keratinocyte; mitogens; protein kinase

Proliferation of the BALB/MK keratinocyte cell line is exquisitely dependent on the complementary action of epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-1). While confluent monolayers synthesize DNA in response to added EGF, sparse cultures that minimize autocrine stimulation have an absolute requirement for both growth factors. A newly defined growth factor isolated in our group, keratinocyte growth factor (KGF), substitutes fully for the EGF requirement indicating that these two growth factors share a common major signal transduction pathway. EGF and IGF-1 are required at distinct points in the cell cycle. EGF drives cells from the quiescent state to a point in mid-Gl. after which it is no longer required. TGF-1, on the other hand, acts after this point to stimulate progression to S-phase. These results indicate that EGF and IGF-1 are not directly interacting, but regulate separate signal transduction events. Synthesis of the CDC-2 histone Hl kinase in quiescent cells is stimulated by triggering with EGF and IGF-1. Ongoing work on CDC-2 will include analysis of growth factor requirements for activation of its kinase activity and subsequent mitotic initiation.

BALB/MK角质形成细胞系的增殖是精细的， 依赖于表皮生长因子（EGF）的互补作用， 胰岛素样生长因子-I（IGF-1）。当汇合的单层细胞合成 DNA响应添加EGF，稀疏的文化，最大限度地减少自分泌 刺激对两种生长因子都有绝对需求。一个新 在我们的小组中分离出一种确定的生长因子，角质细胞生长因子 (KGF)这两种EGF的功效都是一样的， 生长因子共享共同的主要信号转导途径。 EGF和IGF-1在细胞周期的不同时刻都是必需的。EGF驱动 细胞从静止状态到G1中期的某个点。在那之后， 需要更长时间。另一方面，TGF-1在这一点之后起作用， 刺激进展到S期。这些结果表明，EGF和IGF-1 不直接相互作用，但调节单独的信号转导 事件 刺激静止细胞中CDC-2组蛋白Hl激酶的合成 EGF和IGF-1的作用。正在进行的CDC-2工作将包括 分析激活其激酶所需的生长因子 活性和随后的有丝分裂起始。