Gαs promotes EEA1 endosome maturation and shuts down proliferative signaling through interaction with GIV (Girdin).

The organization of the endocytic system into biochemically distinct subcompartments allows for spatial and temporal control of the strength and duration of signaling. Recent work has established that Akt cell survival signaling via the epidermal growth factor receptor (EGFR) occurs from APPL early endosomes that mature into early EEA1 endosomes. Less is known about receptor signaling from EEA1 endosomes.

SPIN90-IRSp53 complex participates in Rac-induced membrane ruffling.

SPIN90 is a key regulator of actin cytoskeletal organization. Using the BioGRID(beta) database (General Repository for Interaction Datasets), we identified IRSp53 as a binding partner of SPIN90, and confirmed the in vivo formation of a SPIN90-IRSp53 complex mediated through direct association of the proline-rich domain (PRD) of SPIN90 with the SH3 domain of IRSp53. SPIN90 and IRSp53 positively cooperated to mediate Rac activation, and co-expression of SPIN90 and IRSp53 in COS-7 cells led to the complex formation of SPIN90-IRSp53 in the leading edge of cells.

The 31-kDa caspase-generated cleavage product of p130cas functions as a transcriptional repressor of E2A in apoptotic cells.

In response to integrin receptor binding to the extracellular matrix, the multidomain docking protein p130(cas) (Crk-associated substrate) activates various signaling cascades modulating such cellular processes as proliferation, migration, and apoptosis. During apoptosis, caspase-mediated cleavage of p130(cas) generated a C-terminal 31-kDa fragment (31-kDa) and promoted morphological changes characteristic of apoptosis, including loss of focal adhesions, cell rounding, and nuclear condensation and fragmentation. By contrast, a p130(cas) D748E mutant, which was unable to produce 31-kDa, attenuated the disassembly of focal adhesions at the bottom of the cell.