Tyrosine phosphorylation of Grb14 by Tie2
- PDF / 776,326 Bytes
- 7 Pages / 595.276 x 793.701 pts Page_size
- 23 Downloads / 173 Views
RESEARCH
Open Access
Tyrosine phosphorylation of Grb14 by Tie2 Celina Sturk1,2, Daniel J Dumont1,2*
Abstract Background: Growth factor receptor bound (Grb) proteins 7, 10 and 14 are a family of structurally related multidomain adaptor proteins involved in a variety of biological processes. Grb7, 10 and 14 are known to become serine and/or threonine phosphorylated in response to growth factor (GF) stimulation. Grb7 and 10 have also been shown to become tyrosine phosphorylated under certain conditions. Under experimental conditions Grb7 is tyrosine phosphorylated by the Tie2/Tie-2/Tek angiogenic receptor tyrosine kinase (RTK). Furthermore, Grb14 has also been shown to interact with Tie2, however tyrosine phosphorylation of this Grb family member has yet to be reported. Results: Here we report for the first time tyrosine phosphorylation of Grb14. This phosphorylation requires a kinase competent Tie2 as well as intact tyrosines 1100 and 1106 (Y1100 and Y1106) on the receptor. Furthermore, a complete SH2 domain on Grb14 is required for Grb14 tyrosine phosphorylation by Tie2. Grb14 was also able to become tyrosine phosphorylated in primary endothelial cells when treated with a soluble and potent variant of the Tie2 ligand, cartilage oligomeric matrix protein (COMP) Ang1. Conclusion: Our results show that Grb14, like its family members Grb7 and Grb10, is able to be tyrosine phosphorylated. Furthermore, our data indicate a role for Grb14 in endothelial signaling downstream of the Tie2 receptor.
Background Signal transduction pathways encompass a series of highly coordinated events involving numerous proteins, varying in both structure and function. Adaptor proteins play a pivotal role in such molecular networks by allowing formation of protein complexes via interactions involving their non-catalytic binding domains. The Growth factor Receptor Bound (Grb) adaptor proteins are a group of structurally similar proteins beginning to emerge as key players in a number of cellular functions including cell metabolism, cell survival and cell migration. The Grb family is made up of three members, Grb7,10 and 14. All family members harbor an amino-terminal proline rich region (PRR), a putative Ras associating (RA) domain, a pleckstrin homology (PH) domain and a carboxyl-terminal SH2 domain. Furthermore, unique to this family of proteins is a novel interaction region, the BPS (for Between PH and SH2) domain. To date the * Correspondence: [email protected] 1 Molecular and Cellular Biology Research, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada Full list of author information is available at the end of the article
BPS domain has been shown to play a role in certain Grb/receptor interactions including those involving the activated Insulin receptor (IR) and Insulin-like Growth Factor Receptor [1]. While all three family members were originally cloned in screens using the EGFR as bait, as with most other SH2 containing proteins it was quickly discovered that this family of adaptors binds
Data Loading...
