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Identification of a Src kinase SH3 binding site in the C‐terminal domain of the human ErbB2 receptor tyrosine kinase
Author(s) -
Bornet Olivier,
Nouailler Matthieu,
Feracci Michaël,
Sebban-Kreuzer Corinne,
Byrne Deborah,
Halimi Hubert,
Morelli Xavier,
Badache Ali,
Guerlesquin Françoise
Publication year - 2014
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2014.04.029
Subject(s) - sh3 domain , proto oncogene tyrosine protein kinase src , tyrosine protein kinase csk , fyn , tyrosine kinase , receptor tyrosine kinase , sh2 domain , protein kinase domain , microbiology and biotechnology , chemistry , cancer research , biology , signal transduction , biochemistry , gene , mutant
Overexpression of the ErbB2 receptor tyrosine kinase is associated with most aggressive tumors in breast cancer patients and is thus one of the main investigated therapeutic targets. Human ErbB2 C‐terminal domain is an unstructured anchor that recruits specific adaptors for signaling cascades resulting in cell growth, differentiation and migration. Herein, we report the presence of a SH3 binding motif in the proline rich unfolded ErbB2 C‐terminal region. NMR analysis of this motif supports a PPII helix conformation and the binding to Fyn‐SH3 domain. The interaction of a kinase of the Src family with ErbB2 C‐terminal domain could contribute to synergistic intracellular signaling and enhanced oncogenesis.