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NTAKalpha and beta isoforms stimulate breast tumor cell growth by means of different receptor combinations.

Neural- and thymus-derived activator for ErbB kinases (NTAK) is a recently described member of the neuregulin family that binds directly to ErbB3 and ErbB4 and transactivates ErbB2. Rat NTAK has at least five alternative-spliced isoforms: alpha1, alpha2a, alpha2b, beta, and gamma. In order to understand their biological properties, this study focused on the NTAK alpha2a and beta isoforms, which have different EGF-like domains. The effect of these isoforms on cell growth and tyrosine phosphorylation in human breast cancer cells, MDA-MB-453 and T47D, was examined using the recombinant proteins. In terms of cell growth, NTAKalpha2a and NTAKbeta preferentially stimulate T47D cells and MDA-MB-453 cells, respectively, in a dose-dependent manner. Although both NTAKs induce the highest level of tyrosine phosphorylation of ErbB2, NTAKalpha2a and NTAKbeta preferentially induce ErbB3 and ErbB4 phosphorylation, respectively. Thus, NTAKalpha2a and NTAKbeta stimulate cell growth in different ways, by means of different combinations of receptors.