The Ras-ERK pathway regulates a variety of cellular and physiological responses, including cell proliferation, differentiation, morphogenesis during animal development, and homeostasis in adults. Deregulated activation of this pathway leads to cellular transformation and tumorigenesis as well as RASopathies. Several negative regulators of this pathway have been documented. Each of these proteins acts at particular points of the pathway, and they exert specific cellular and physiological functions. Among them, DA-Raf1 (DA-Raf), which is a splicing isoform of A-Raf and contains the Ras-binding domain but lacks the kinase domain, antagonizes the Ras-ERK pathway in a dominant-negative manner. DA-Raf induces apoptosis, skeletal myocyte differentiation, lung alveolarization, and fulfills tumor suppressor functions by interfering with the Ras-ERK pathway. After the findings of DA-Raf, several kinase-domain-truncated splicing variants of Raf proteins have also been reported. The family of these truncated proteins represents the concept that alternative splicing can generate antagonistic proteins to their full-length counterparts.

中文翻译：

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Ras-ERK途径的主要阴性拮抗剂：DA-Raf及其相关蛋白，是通过Raf的可变剪接产生的。

Ras-ERK途径调节多种细胞和生理反应，包括细胞增殖，分化，动物发育过程中的形态发生以及成人体内的稳态。该途径的激活失控导致细胞转化和肿瘤发生以及RASopathies。已经记录了该途径的一些负面调节剂。这些蛋白质中的每一种都在该途径的特定点起作用，并且发挥特定的细胞和生理功能。其中，DA-Raf1（DA-Raf）是A-Raf的一个剪接同工型，包含Ras结合结构域，但缺少激酶结构域，以显性负性方式拮抗Ras-ERK途径。DA-Raf诱导细胞凋亡，骨骼肌细胞分化，肺泡形成，并通过干扰Ras-ERK途径来发挥抑癌功能。在发现DA-Raf之后，也已经报道了Raf蛋白的几种激酶结构域截短的剪接变体。这些截短的蛋白质家族代表了这样的概念，即选择性剪接可以产生与其全长对应物相对的拮抗蛋白质。