N-terminal Domains of the Class IA Phosphoinositide 3-Kinase Regulatory Subunit Play a Role in Cytoskeletal but not Mitogenic Signaling

23Citations
Citations of this article
22Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Phosphoinositide (PI) 3-kinases are required for the acute regulation of the cytoskeleton by growth factors. We have shown previously that in the MTLn3 rat adenocarcinoma cells line, the p85/p110α PI 3-kinase is required for epidermal growth factor (EGF)-stimulated lamellipod extension and formation of new actin barbed ends at the leading edge of the cell. We have now examined the role of the p85α regulatory subunit in greater detail. Microinjection of recombinant p85α into MTLn3 cells blocked both EGF-stimulated mitogenic signaling and lamellipod extension. In contrast, a truncated p85(1-333), which lacks the SH2 and iSH2 domains and does not bind p110, had no effect on EGF-stimulated mitogenesis but still blocked EGF-stimulated lamellipod extension. Additional deletional analysis showed that the SH3 domain was not required for inhibition of lamellipod extension, as a construct containing only the proline-rich and breakpoint cluster region (BCR) homology domains was sufficient for inhibition. Although the BCR domain of p85 binds Rac, the effects of the p85 constructs were not because of a general inhibition of Rac signaling, because sorbitol-induced JNK activation in MTLn3 cells was not inhibited. These data show that the proline-rich and BCR homology domains of p85 are involved in the coupling of p85/p110 PI 3-kinases to regulation of the actin cytoskeleton. These data provide evidence of a distinct cellular function for the N-terminal domains of p85.

Cite

CITATION STYLE

APA

Hill, K. M., Huang, Y., Yip, S. C., Yu, J., Segall, J. E., & Backer, J. M. (2001). N-terminal Domains of the Class IA Phosphoinositide 3-Kinase Regulatory Subunit Play a Role in Cytoskeletal but not Mitogenic Signaling. Journal of Biological Chemistry, 276(19), 16374–16378. https://doi.org/10.1074/jbc.M006985200

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free