ERK1 associates with alpha(v)beta 3 integrin and regulates cell spreading on vitronectin.
Kinases that associate with integrins are likely to mediate the assembly/disassembly of cell:matrix junctions during cell migration. Here we show that ERK1 associates with alpha(v)beta(3) integrin following the addition of platelet-derived growth factor to serum-starved Swiss or NIH 3T3 fibroblasts in an interaction that is mediated by the central region of the beta(3) integrin cytodomain. alpha(v)beta(3).ERK1 association occurred prior to focal complex formation and was seen to initiate in small punctate complexes primarily in the peripheral regions of the plasma membrane. Expression of a dominant negative mutant of ERK1 (but not ERK2) significantly reduced the spreading of cells on vitronectin, whereas cell spreading on fibronectin was unaffected by inhibition of ERK1. In contrast, inhibition of ERK activation by PD98059 had no effect on the platelet-derived growth factor-regulated Rab4-dependent flux of alpha(v)beta(3) integrin from early endosomes to the plasma membrane, an event that is also necessary for cells to spread efficiently on vitronectin. We propose that alpha(v)beta(3) integrin must recycle to the plasma membrane via the Rab4 pathway and recruit active ERK1 in order to function efficiently.
Roberts
Marnie S
MS
Department of Biochemistry, University of Leicester, University Road, Leicester LE1 7RH, United Kingdom.
Woods
Alison J
AJ
Shaw
Peter E
PE
Norman
Jim C
JC
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D004789:Enzyme Activation; D005419:Flavonoids / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D019096:Vitronectin / Q000378:metabolism*
D005419:Flavonoids; D039302:Integrin alphaVbeta3; D019096:Vitronectin; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one