Faculty Profiles

 

Current Research:
SH2-b b is a widely expressed protein that binds, via its SH2 domain, to the activated form of multiple receptor tyrosine kinases, including receptors for PDGF, nerve growth factor, insulin, insulin-like growth factor and to cytoplasmic tyrosine kinase JAK2. We have previously implicated SH2-Bbeta in GH and PDGF regulation of the actin cytoskeleton . We have also implicated SH2-Bbeta in direct regulation of actin-dependent cell motility and shown that the proline-rich region of SH2-Bbeta is required for binding of SH2-Bbeta to the actin-regulating small GTPase Rac (Diakonova et al., 2002). We proposed that SH2-Bbeta acts as an adapter or scaffolding protein that recruits actin-regulating proteins to membrane cytokine and growth factor receptors. Current understanding of actin-based motility is founded on many years of observation, but has been benefited greatly from studies on intracellular motility of bacteria Listeria. My recent data indicate that SH2-B b plays an important role in the regulation of Listeria actin-dependent motility. The goal of my current project is to determine the mechanism by which SH2-B b increases the motility of Listeria. We examine the hypothesis that SH2-B b plays an essential role in Listeria motility and distribution by recruiting actin-regulating proteins from the host cell's cytoplasm to sites of active actin polymerization.

Representative Publication:
Diakonova M., B.Payrastre, A.van Velzen, W.J. Hage,P.van Bergen en Henegouwen, J.Boonstra, F.Cremers,B.Humbel. "EGF Induces Rapid and Transient Association of PLC g1 with EGF-Receptor and Filamentous Actin at Membrane Ruffles of A431 Cells." Journal of Cell Science, 108, 2499-2509, 1995

 

Diakonova M., Chilov D., Arnautov A., Alexseyev V., Nikolsky N., Medvedeva N. "Intracellular Distribution of PLCg1 in Cell Lines with Different Level of Transformation." Europ. J. Cell. Biol., 73, 360-367, 1997

 

Diakonova M., Gerke V., Ernst J., Liautard J.-P., van der Vusse,G., Griffiths G. "Localization of Five Annexins in J774 Macrophages and on Isolated Phagosomes." Journal of Cell Science, 110, 1199-1213, 1997

 

Defacque H., M. Egeberg, A. Huberman, M. Diakonova, C. Roy, P. Mangeat, W. Voelter, G. Marriott, J. Pfannsteil, H. Faulstich, G. Griffiths."Involvement of Ezrin/moesin in de Novo Actin Assembly on Phagosomal Membranes." The EMBO, J., 19, 199-212, 2000.

 

Diakonova M., J. Herrington, L. Rui, D. Gunter, C. Carter-Su. "SH2-Bbeta is Required for Growth Hormone-Induced Actin Reorganization." J. Biological Chemistry, 275, 13126-13133, 2000.

 

Carter-Su C., L. Rui, J. Herrington, M. Stofega, M. Diakanova. "Growth Hormone Signaling Pathways. In Targets for Growth Hormone and IGF-1 Action Ed. R. Bouillon, 1-13, BioScienfica Ltd, Bristol, 2001

 

Diakonova M., G. Bokoch, J.A. Swanson. "Dynamics of Cytockeleta Proteins During Fcgamma-Receptor-Mediated Phagocytosis in Macrophages." Mol. Biol. of Cell, 13, 402-411, 2002.

 

Diakonova M., D. R. Gunter, J. Herrington, C.Carter-Su. "SH2-Bbeta is a Rac Binding Protein that Regulates Cell Motility." Journal Biological Chemistry, 277, 10669-10677, 2002.

 

O'Brien KB., L.S. Argetsinger, M. Diakonova, C. Carter-Su. 'YXXL Motifs in SH2-Bbeta are Phosphorylated by JAK2, JAK1, and Platelet-Derived Growth Factor Receptor and are Required for Membrane Ruffling." J. Biol. Chem, 278, 11970 - 11978, 2003

 

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