title: The homolog of the five SH3-domain protein (HOFI/SH3PXD2B) regulates lamellipodia formation and cell spreading.
abstract: Motility of normal and transformed cells within and across tissues requires specialized subcellular structures, e.g. membrane ruffles, lamellipodia and podosomes, which are generated by dynamic rearrangements of the actin cytoskeleton. Because the formation of these sub-cellular structures is complex and relatively poorly understood, we evaluated the role of the adapter protein SH3PXD2B [HOFI, fad49, Tks4], which plays a role in the development of the eye, skeleton and adipose tissue. Surprisingly, we find that SH3PXD2B is requisite for the development of EGF-induced membrane ruffles and lamellipodia, as well as for efficient cellular attachment and spreading of HeLa cells. Furthermore, SH3PXD2B is present in a complex with the non-receptor protein tyrosine kinase Src, phosphorylated by Src, which is consistent with SH3PXD2B accumulating in Src-induced podosomes. Furthermore, SH3PXD2B closely follows the subcellular relocalization of cortactin to Src-induced podosomes, EGF-induced membrane ruffles and lamellipodia. Because SH3PXD2B also forms a complex with the C-terminal region of cortactin, we propose that SH3PXD2B is a scaffold protein that plays a key role in regulating the actin cytoskeleton via Src and cortactin.
authors: Department of Immunology, University of Debrecen Medical and Health Science Center, Debrecen, Hungary. alanyi@dote.hu
authors: Árpád
authors: Á
authors: Lányi
authors: Mónika
authors: M
authors: Baráth
authors: Zalán
authors: Z
authors: Péterfi
authors: Gábor
authors: G
authors: Bogel
authors: Anna
authors: A
authors: Orient
authors: Tünde
authors: T
authors: Simon
authors: Eniko
authors: E
authors: Petrovszki
authors: Katalin
authors: K
authors: Kis-Tóth
authors: Gábor
authors: G
authors: Sirokmány
authors: Éva
authors: É
authors: Rajnavölgyi
authors: Cox
authors: C
authors: Terhorst
authors: László
authors: L
authors: Buday
authors: Miklós
authors: M
authors: Geiszt
mesh_terms: D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D002465:Cell Movement; D051356:Cortactin / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006367:HeLa Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D011554:Pseudopodia / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D018909:src Homology Domains
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; C495868:CTTN protein, human; D051356:Cortactin; D010716:Phosphatidylinositols; C547814:SH3PXD2B protein, human; D066246:ErbB Receptors