Life Sciences Commons^™

Integrin-Linked Kinase Modulation Of Melanocytic Lineage Cells, Melissa Crawford

Electronic Thesis and Dissertation Repository

Melanocytes are specialized melanin-producing cells found in the skin, inner ear and heart. Melanocyte abnormalities cause many human disorders, including pigmentation defects, deafness, and melanoma. A better understanding of melanocyte biology is essential to address those disorders. Integrin-linked kinase (ILK) is a ubiquitous scaffold protein, essential for epidermal development. Importantly, the mechanisms by which ILK modulates the development and functions of melanocytic lineage cells remains unknown. To help address this void, I have developed cell-based models, as well as a reporter mouse model that allows tamoxifen-inducible Ilk gene inactivation specifically in melanocytic cells.

I observed that inactivation of Ilk in …

Role Of Integrin-Linked Kinase In Epidermal Integrity And Barrier Function, Samar Sayedyahossein

Electronic Thesis and Dissertation Repository

Integrin-linked kinase (ILK) is a β integrin adaptor protein that translates extracellular stimuli to intracellular signaling events. ILK plays a role in actin cytoskeleton dynamics and cell adhesion. The structure and function of the epidermis is highly dependent on cell-cell adhesion and cell-basement membrane interactions. The mechanisms whereby ILK contributes to epidermal integrity are poorly understood. Using a mouse model of epidermis-restricted Ilk gene inactivation, I observed that ILK loss causes abnormal morphology and presence of intra-epidermal and epidermal-dermal microblisters in embryos as early as E17.5. ILK-deficient epidermis is also characterized by abnormal localization or/and absence of adherens junctions, tight …

A Rhog/Ilk/Elmo2/Rac1 Pathways Modulates Microtubule Stability, Bradley C. Jackson

Electronic Thesis and Dissertation Repository

Integrin-linked kinase (ILK) is a widely expressed scaffold protein important for cell adhesion, migration, and phagocytosis. ILK and its interacting partner, engulfment and cell motility protein 2 (ELMO2), may also modulate microtubule dynamics. Here, I show that sustained microtubule growth and acetylated tubulin levels are reduced in the absence of ILK and, conversely, that exogenous ILK exerts a stabilizing effect on microtubules. Further, exogenous ELMO2, ras homology growth related protein (RHOG) and ras-related C3 botulinum toxin substrate 1 (RAC1) stabilize microtubules in an ILK-dependent manner. Potential downstream effectors of the effect of ILK on microtubule stability include glycogen synthase kinase- …

Transforming Growth Factor-Beta Receptor Signalling Is Modulated By Integrin-Linked Kinase, Stellar H. Boo

Electronic Thesis and Dissertation Repository

Transforming growth factor-beta 1 (TGF-β1) modulates regeneration after injury through induction of fibroblast proliferation, migration, and differentiation into myofibroblasts. Induction of myofibroblast differentiation by TGF-β1 requires expression of integrin-linked kinase (ILK). I now show that ILK interacts with TGF-β receptor type II (TβRII) in primary dermal fibroblasts. Further, colocalization of ILK and TβRII can be observed at the cell membrane and in intracellular vesicles. The association of TβRII and ILK does not require TGF-β1 stimulation, kinase activity of TGF-β1 receptor type I or TβRII, and it does not involve interactions between ILK and focal adhesion-associated proteins. When this interaction is …