Neuregulin-Induced Association of Sos Ras Exchange Protein with HER2(erbB2)/HER3(erbB3) Receptor Complexes in Schwann Cells through a Specific Grb2-HER2(erbB2) Interaction

Abstract

Neuregulins are members of the epidermal growth factor family of related ligands that exert pleotropic effects during development on the Schwann cell lineage. The receptor complex activated by neuregulin in Schwann cells consists of HER2 (erbB2) and HER3 (erbB3). The intracellular signaling events that follow activation of the HER2/HER3 receptor complex in primary cells, and in particular in Schwann cells, are poorly understood. We have found that neuregulin induces the rapid association of the guanine nucleotide exchange factor SOS with the HER2/HER3 receptor complex. The association of SOS with the HER2/HER3 receptor complex is preceded by the rapid association of Grb2 with the HER2/HER3 receptor complex. Far Western analysis indicates that Grb2 and SOS bind exclusively to HER2 in the HER2/HER3 receptor complex.

Myopathy caused by HRAS germline mutations: implications for disturbed myogenic differentiation in the presence of constitutive HRas activation

“…Notably, signalling induced by these molecules has been shown to be at least partly dependent upon Ras. [26][27][28] These processes may be perturbed in the presence of constitutively active HRas during skeletal muscle differentiation and eventually lead to excess muscle spindle formation. Further experimental studies are needed to elucidate the precise underlying mechanisms.…”

The role of cytology in oral lesions: A review of recent improvements

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The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesis

“…Even chimeric kinase-active HER3 constructs fail to signal without hetero-partners suggesting that HER3 even lacks the ability to homodimerize and is an obligate heterodimerization partner (Berger et al, 2004). Although individually they are incomplete signaling molecules, a large body of evidence not only establishes HER2 and HER3 as obligate partners but their complex forms the most active signaling heterodimer of the family and essential for many biologic and developmental processes (Sliwkowski et al, 1994;Horan et al, 1995;Wallasch et al, 1995b;Tzahar et al, 1996;Britsch et al, 1998;Keely and Barrett, 1999;Vartanian et al, 2000;Goodearl et al, 2001;Vijapurkar et al, 2003). The HER proteins are widely expressed and functionally important in non-hematopoietic tissues (Real et al, 1986;Press et al, 1990).…”