RaplA protein

Insight into the molecular interaction between Raf kinase and Ras protein was obtained from the crystal structure of the complex between the Ras binding domain of c-Rafl kinase and a Ras-like protein, RaplA protein (Nassar et al., 1995, review Wit-tinghofer and Nassar, 1996). 

The structure of the complex indicates a specific interaction between P-sheet structures of Raf kinase and structural elements of RaplA protein belonging to the switch I region, which are thus part of the RaplA protein effector domain. Since RaplA protein has a very similar structure to Ras protein, it is assumed that Ras protein also interacts with Raf kinase via its switch I region. 

Two structural elements of the Raf kinase have been found to interact with the Ras protein. One structural element involved in complex formation on the c-Rafl kinase side is the Ras-binding domain, encompassing amino acids 51-131 of the CR1 domain. On the Ras protein side, the switch I region is involved in this interaction, as shown by the crystal structure of the complex between the Ras-binding domain of c-Rafl kinase and the GTP form of the Ras-like protein, RaplA protein (Nassar et ah, 1995 ). These structural studies did not reveal gross conformational changes of the two proteins upon complex formation. 

The discovery of PLCs reveals a fourth mechanism whereby the enzyme can be activated (Fig. 20-5). PLCs possesses two Ras-binding (RA) domains in its carboxyl terminal region, and occupancy of these by Ras-GTP results in activation of the enzyme. In addition, the enzyme possesses a CDC-25 domain at its N-terminus, which serves as a guanine nucleotide exchange factor (GEF) for small GTP-binding proteins such as Ras or RaplA. Thus PLCe can not only activate the GDP-bound forms of these small GTP-binding proteins but can also be... 

Ki-ras and N-ras. Expression of rapl A (also known as Krev-1) causes the reversion of cells that have been transformed by Ki-ras, and so the function of p21 raplA may counteract the action of ras proteins. 

The Rap (Ras proximate) proteins, Rapla and Raplb, and Rap2a/b/c, belong to the Ras subfamily of small GTPases, sharing 50% sequence similarity with Ras [22]. Rap proteins function primarily in cell adhesion and migration, and polarity [23,24]. Rapla (CAAX = CLLL) is 95%... 

KLINZ FJ, SEIFERT R, SCHWANER I, GAUSEPOHL H, FRANK R, SCHULTZ G (1992) Generation of spedlic antibodies against the raplA, raplB and rap2 small GTP-binding proteins Andysis of rap and ras proteins in membranes from manamalian cdls. European Journal of Biochemistry, 207,207-213. 

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