department of pharmacology

Jun Qin, Ph.D.



School of Medicine
Case Western Reserve University

Department of Molecular
Lerner Research Institute
The Cleveland Clinic Foundation

9500 Euclid Avenue
Cleveland, Ohio 44195

Phone: (216) 444-5392
Fax: (216) 445-1466


The primary research aim of our laboratory is to probe and understand the molecular mechanisms of key biological events involving biomolecular interactions, notably protein-protein and protein-nucleic acid interactions. The major step towards this goal is the study of three dimensional structures and dynamics of proteins and protein complexes at atomic resolution. Our laboratory is engaged in this study by using state-of-the-art nuclear magnetic resonance spectroscopy (NMR) as a primary tool, combined with other modern biology techniques. Several projects have been ongoing in the laboratory including (a) receptor mediated signal transduction such as integrin signaling and ion-channel; (b) mechanistic investigation of integrin-linked kinase (ILK) and protein kinase R (PKR) involved in cellular signaling. The current major focus is to explore the molecular basis of integrin signaling involved in regulating cell adhesion and cell migration.

Integrins are known to be heterodimeric α/β cell surface receptors that mediate adhesion of the cells to one another and to their surroundings. Such adhesion is crucial for many biological processes, such as embryogenesis, haemostasis, the immune response and the maintenance of tissue integrity; and its dysfunction leads to numerous human disorders such as thrombasthenia and chronic inflammatory diseases. Therefore, understanding the mechanism of integrin adhesion is of both physiological and pathological importance. The integrin’s ability to bind their extracellular ligands for adhesion is tightly regulated through a process termed inside-out signaling, i.e., a cellular signal stimulates a conformational change in the cytoplasmic domain of an integrin, which propagates through its transmembrane region to the extracellular domain, transforming it from a low to a high affinity ligand binding state (integrin activation). On the other hand, ligand occupancy of the extracellular domain also elicits signals back to the cytoplasmic face, which activate cascades of intracellular responses ultimately connecting to cytoskeleton (outside-in signaling). In this manner, the inside and outside of the cells are physically linked, resulting in a cooperative regulation of cell functions including cell adhesion, migration, cell growth and differentiation. While the cytoplasmic domains of integrins are small and devoid of enzymatic activities, they are the center of bi-directional signaling machinery and hence crucial for the control of the integrin function. Our goal in this study is to elucidate the structural basis of the integrin bi-directional signaling as mediated by the cytoplasmic domains. A working hypothesis is that the cytoplasmic face adopts distinct conformations that direct the inside-out and outside-in signaling processes. We are pursuing the structure of the δIibβ3 cytoplasmic complex and its interactions with the intracellular signaling network. We are also pursuing the structure determination of integrin cytoplasmic domain coupled with the transmembrane domain. These structures will provide atomic insights into the complex mechanism of integrin activation and signaling.


Velyvis A, Vaynberg, J., Yang, Y., Vinogradova O, Zhang, Y., Wu, C., Qin J. Structural and functional insights into PINCH LIM4 domain-mediated integrin signaling Nature Struct. Biol. 10, 558-564, 2003.

Vinogradova, O., Velyviene, A., Velyvis, A., Haas, T., Plow, E.F., and Qin, J. A structural mechanism of integrin ?IIb?3 ‘inside-out’ activation as regulated by its cytoplasmic face. Cell, 110, 587-597. 2002

Shi, Y., Krishnamoorthy, G., Yang, Y., Hu, L., Chaturvedi, N., Harilal, D., Qin, J. and Cui, J. Mechanism of magnesium activation of calcium-activated potassium channels. Nature, 418:876-880, 2002.

Velyvis, A., Yang, Y., Rahman, F., and Qin, J. Solution Structure of Focal Adhesion Adaptor PINCH LIM1 Domain and Its Interaction with the Ankyrin Repeat Domain of Integrin-linked Kinase. J. Biol. Chem. 276:4932-4939, 2001.

Vinogradova, O., Haas, T., Plow, E.F., and Qin, J. A Structural Basis for Integrin Activation by the Cytoplasmic Tail of the ?IIb Subunit. Proc. Natl. Acad. Sci, 76, 1450-55, 2000.

Nanduri, S., Rahman, F., Williams, BRG, and Qin, J. A dynamically-tuned double stranded RNA binding mechanism for the activation of antiviral protein kinase PKR. EMBO J., 19, 5567-5574, 2000.