• Fumio Matsumura
  • Fumio Matsumura
  • Professor
  • Department: Deptartment of Molecular Biology and Biochemistry
  • Phone: 1.8484452838
  • Rutgers University
  • Nelson Hall, A321
  • Piscataway, NJ 08854
  • Key Words: Control of cell division, microfilaments, cytokinesis, protein phosphorylation, cell transformation

Cell division is central to the life of all multicellular organisms. Our research is aimed at understanding how animal cultured cells divide. At mitosis, normal adherent cells become rounded during prophase and microfilament bundles (stress fibers) are disassembled. Focal adhesions, a specialized structure for cell adhesions, to which microfilament bundles anchor, are also disrupted, causing reduced adhesion to extracellular matrix (ECM) and inactivation of focal adhesion-mediated signal transduction. After cytokinesis, daughter cells reverse the process of these morphological alterations. These cyclic changes in cell shape and adhesions are critical for the proliferation of normal adherent cells. For example, if cell spreading and attachment during G1 is blocked, the cell cycle of normal cells is arrested. In contrast, the proliferation of many transformed cells apparently does not require cell spreading and attachment to ECM. For the past several years, we have focused on the biological functions of two proteins, the myosin-targeting subunit of myosin phosphatase (MYPT) and focal adhesion kinase (FAK) that, we think, play a crucial role in the reoganizational events of stress fibers and focal adhesions.

MYPT controls phosphorylation of MLC (myosin light chain. a subunit of myosin II) by activating myosin phosphatase. Because phosphorylation levels of MLC determine the activity of myosin II (a motor protein responsible for cytokinesis), MYPT may be a key protein to control cytokinesis. We have demonstrated that MYPT is phosphorylated in a mitosis-specific way, resulting in the activation of MYPT during mitosis. We hypothesize that this activation may cause dephosphorylation of MLC and disassembly of stress fibers during prophase.

FAK is a tyrosine kinase prominently localized at focal adhesions and appears to be a primary mediator of integrin-mediated signal transduction. We have discovered that FAK is serine phosphorylated in a mitosis-specific way. This serine phosphorylation (but not tyrosine phosphorylation) causes the dissociation of FAK from CAS, which may result in inactivation of the FAK-mediated signaling. One effect of the inactivation may be the inhibition of cell spreading and migration during mitosis because FAK/CAS association has been implicated as a mediator of cell spreading and migration. Another possibility is that the FAK inactivation may block signals initiating apoptosis that might otherwise be triggered by cell detachment during mitosis. We will examine these possibilities by expressing mutant FAKs lacking mitosis-specific phosphorylation sites.