| First Author | Diakonova M | Year | 2002 |
| Journal | J Biol Chem | Volume | 277 |
| Issue | 12 | Pages | 10669-77 |
| PubMed ID | 11786545 | Mgi Jnum | J:75465 |
| Mgi Id | MGI:2176658 | Doi | 10.1074/jbc.M111138200 |
| Citation | Diakonova M, et al. (2002) SH2-Bbeta Is a Rac-binding Protein That Regulates Cell Motility. J Biol Chem 277(12):10669-77 |
| abstractText | The Src homology 2 (SH2) domain-containing protein SH2-Bbeta binds to and is a substrate of the growth hormone (GH) and cytokine receptor-associated tyrosine kinase JAK2. SH2-Bbeta also binds, via its SH2 domain, to multiple activated growth factor receptor tyrosine kinases. We have previously implicated SH2-Bbeta in GH and platelet-derived growth factor regulation of the actin cytoskeleton. We extend these findings by establishing a potentiating effect of SH2-Bbeta on GH-dependent cell motility and defining regions of SH2-Bbeta required for this potentiation. Time-lapse video microscopy, phagokinetic, and/or wounding assays demonstrate reduced movement of cells overexpressing SH2-Bbeta lacking an intact SH2 domain because of a point mutation or a C-terminal truncation. An N-terminal proline-rich domain (amino acids 85-106) of SH2-Bbeta is required for inhibition of cellular motility by SH2 domain-deficient mutants. Co-immunoprecipitation experiments indicate that Rac binds to this domain. GH is shown to activate endogenous Rac, and dominant negative mutants of SH2-Bbeta are shown to inhibit membrane ruffling induced by constitutively active Rac. These findings suggest that SH2-Bbeta is an adapter protein that facilitates actin rearrangement and cellular motility by recruiting Rac and potentially Rac-regulating, Rac effector, or other actin-regulating proteins to activated cytokine (e.g. GH) and growth factor receptors. |
