ERBB2 belongs to the protein kinase superfamily, Tyr protein kinase family and EGF receptor subfamily. It contains a protein kinase domain. ERBB2 is widely expressed in epithelial cells, and amplification and/or overexpression of ErbB2 has been reported associated with malignancy and a poor prognosis in numerous carcinomas, including breast, prostate and ovarian cancers. Rat ERBB2 is an essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. ErbB2 mediates signalling pathways which involve mitogen-activated protein kinase and phosphatidylinositol-3 kinase, this receptor plays a key role in development, cell proliferation and differentiation.

MST4, also known as mammalian STE2-like protein kinase 4, is a novel member of the germinal center kinase subfamily of human Ste2-like kinases and is closely related to MST3. The 416 amino acid full-length MST4 contains a C-terminal regulatory domain and an N-terminal kinase domain, both of which are required for full activation of the kinase. MST4 is highly expressed in the placenta, thymus, and peripheral blood leukocytes. MST4 specifically activates ERK but not JNK or p38 MAPK in transiently transfected cells or stable cell lines, and thus is biologically active in the activation of the MEK/ERK pathway mediating cell growth and transformation. Further, MST4 kinase activity is stimulated significantly by epidermal growth factor receptor (EGFR) ligands, which are known to promote the growth of certain cancer cells. Accordingly, MST4 has a potential role in signal transduction pathways involved in cancer progression. Three alternatively spliced isoforms of MST4 have been isolated, and isoform 3 lacks an exon encoding kinase domain and may function as a dominant-negative regulator of the MST4 kinase.

Amphiregulin (AREG) is a single-pass membrane protein with 252 amino acids. AREG belongs to the amphiregulin family, which contains 1 EGF-like domain. AREG is expressed in a variety of tissues including ovary, placenta, lung, kidney, stomach, colon, and breast. It is related to Epidermal Growth Factor (EGF) and Transforming Growth Factor Alpha (TGF-alpha). As an EGF-related growth factor, AREG interacts with the EGF/TGF-alpha receptor to promote the growth of normal epithelial cells and inhibits the growth of certain aggressive carcinoma cell lines. AREG may also play a protective role in Bleomycin-Induced Pneumopathy.