The @entity462 -rich sprouty translocation domain targets mitogen-activated protein kinase inhibitory proteins to XXXX in plasma membranes.

@entity1 @entity462 @entity17418 @entity1078 @entity19 @entity5743 @entity1360 @entity669
Sprouty (Spry) proteins have been revealed as inhibitors of the Ras/mitogen-activated protein kinase (MAPK) cascade, a pathway crucial for developmental processes initiated by activation of various receptor @entity669 kinases. In COS-1 and @entity19 cells, all Spry isoforms translocate to the plasma membrane, notably ruffles, following activation. Here we show that microinjection of active Rac induced the translocation of Spry isoforms, indicating that the target of the Spry translocation domain (SpryTD) is downstream of active Rac. Targeted disruption of actin polymerization revealed that the SpryTD target appeared upstream of cytoskeletal rearrangements. Accumulated evidence indicated that @entity1078 [ @entity17418 ] is the likely SpryTD target. @entity1 Spry2TD (hSpry2TD) binds to @entity17418 in vesicle-binding assays. @entity5743 TD colocalizes with the pleckstrin homology domain of phospholipase Cdelta, which binds @entity17418 . The plasma membrane localization of @entity5743 TD was abolished in @entity1360 -treated MDCK cells or when @entity17418 was specifically dephosphorylated by overexpression of an engineered, green fluorescent protein-tagged inositol 5-phosphatase. Similarly, Spred, a novel Ras/MAPK inhibitor recently found to contain the conserved @entity462 -rich SpryTD, also translocated to peripheral membranes and bound to @entity17418 . Alignment of the Spry and Spred proteins led us to identify a translocation-defective point mutant, @entity5743 D252. Targeting of @entity5743 to @entity17418 was shown to be essential for the down-regulation of Ras/MAPK signaling.
