City College of CUNY
Department of Chemistry
Biochemistry Seminar
Wednesday, February 9, 2000
Room J1027
11:15 AM
Professor Jianxun Li
University of Illinois at Chicago
School of Dentistry
Department of Oral Biology
Cytoskeleton and PKC Substrates in
Integrin Activation and Cell Adhesion
ABSTRACT

Cell adhesion and spreading are essential events in many physiological processes including immune responses, cell proliferation and differentiation, as well as in angiogenesis. Integrins, a family of adhesion molecules on the cell surface, play vital roles in these events. For years, the mechanism controlling the interaction of cell surface integrin with the surrounding environment, i.e. integrin activation, has been a key issue in biomedical research. It is now wide believed that cytoskeleton, membrane and membrane-bound receptors form a single unified and inter-dependent entity. But it is not known how cytoskeleton together with cytoskeleton-associated proteins and other signal transduction molecules, such as protein kinase C (PKC) and Ca2+/Calmodulin, control the integrin molecules on the surface of cell membrane.
To activate the ?2 integrin, protein kinase C must first be activated. The PKC signal is then translated into the activation of the surface integrin. This signal transduction event is mediated by the cytoskeleton. The question is how cytoskeleton and which component of the cytoskeleton transduces the PKC signal to regulate the surface receptors. Our research shows that MacMARCKS, a PKC substrate, integrates cytoskeleton, plasma membrane and ?2 integrin into one dynamic entity. MacMARCKS binds to dynamitin, a microtubule-auxiliary protein and regulates the tyrosine phosphorylation of paxillin, a key protein in the focal adhesion. All the above functions are regulated by PKC-mediated phosphorylation of MacMARCKS protein. Through the MacMARCKS-mediated cross-talk between different cytoskeletal components and the lipid membrane, overall fluidity of the cell surface, as well as the motility of surface bound integrin molecules, and possibly the clustering of these integrin molecules are changed so that the integrins are stabilized in a high-avidity state. Each of these events tightly correlates with the concept that the cytoskeleton is not merely a structural support as a beam or a joist, but also an integral part of regulatory system. Models corresponding to this principle based on these findings and the others will be proposed and discussed in detail in the presentation.