p70 S6 kinase and actin dynamics: A perspective

Abstract

p70 S6 kinase (p70(S6K)), a member of the AGC serine/threonine kinase family, was initially identified as a key player, together with its downstream effector S6, in the regulation of cellular growth and survival. The p70(S6K) protein has emerged in recent years as a multifunctional protein which also regulates the actin cytoskeleton and thus plays a role in cell migration. This new function is through two important activities of p70(S6K), namely actin cross-linking and Rac1 and Cdc42 activation. The testis is critically dependent on an intricate balance of fundamental cellular processes such as adhesion, migration, and differentiation. It is increasingly evident that Rho GTPases and actin binding proteins play fundamental roles in regulating spermatogenesis within the testis. In this review, we will discuss current findings of p70(S6K) in the control of actin cytoskeleton dynamics. In addition, the potential role of p70(S6K) in spermatogenesis and testicular function will be highlighted.

Figure 1. A model to illustrate domains and phosphorylation sites of p70^S6K. p70^S6K can be divided into five functional domains/regions: (1) the amino (N)-terminal domain (blue), (2) the AGC-kinase conserved catalytic domain (yellow), (3) the linker region (green), (4) the putative autoinhibitory domain (red), and (5) the carboxyl (C)-terminal domain (purple). Eight phosphorylation sites have been mapped.

Figure 2. Schematic illustration on the mechanism by which p70^S6K regulates actin cytoskeleton in ovarian cancer cells. p70^S6K directly binds/cross links with F-actin and activates PAK1 through Rac1 and Cdc42 to modulate actin cytoskeleton dynamics for cell migration.

Figure 3. Schematic perspective of p70^S6K on spermatogenesis regulation in Sertoli cells. p70^S6K activation through the PI3K/Akt or MAPK pathways may have a possible role in regulating the actin cytoskeleton at AJ and BTB restructuring through Rac1/Cdc42-activating activities.