A5000430069- Cellular Mechanics and Interactions
- Cell Adhesion Molecules Research
- Congenital heart defects research
- Protein Kinase Regulation and GTPase Signaling
- Melanoma and MAPK Pathways
- Wnt/β-catenin signaling in development and cancer
- Congenital Heart Disease Studies
- Ubiquitin and proteasome pathways
- Cancer Mechanisms and Therapy
- interferon and immune responses
- Hippo pathway signaling and YAP/TAZ
- Salivary Gland Disorders and Functions
- Neurofibromatosis and Schwannoma Cases
- Signaling Pathways in Disease
- Genomics and Chromatin Dynamics
- Cancer-related Molecular Pathways
- T-cell and B-cell Immunology
- Cytokine Signaling Pathways and Interactions
- Pluripotent Stem Cells Research
- RNA Research and Splicing
- NF-κB Signaling Pathways
- Cell death mechanisms and regulation
- Galectins and Cancer Biology
- Plant Gene Expression Analysis
- Computational Drug Discovery Methods
University of Chicago
2003-2021
May Institute
1998-2021
Oregon Health & Science University
2002-2010
Howard Hughes Medical Institute
1993-2010
Weatherford College
2008
Molecular Oncology (United States)
1998-2006
Beth Israel Deaconess Medical Center
2006
UConn Health
2003
Centre for Cancer Biology
2003
Tokyo Medical and Dental University
2002
The ROSAβgeo26 (ROSA26) mouse strain was produced by random retroviral gene trapping in embryonic stem cells. Staining of ROSA26 tissues and fluorescence-activated cell sorter-Gal analysis hematopoietic cells demonstrates ubiquitous expression the proviral βgeo reporter gene, bone marrow transfer experiments illustrate general utility this for chimera transplantation studies. trap vector has integrated into a region that produces three transcripts. Two transcripts, lost homozygous animals,...
The integrin family of cell adhesion receptors are important for a diverse set biological responses during development. Although many integrins have been shown to engage similar cytoplasmic effector proteins in vitro, the importance these events mediated by different and ligands is uncertain. We examined role one best-characterized effectors, focal protein paxillin, disruption paxillin gene mice. Paxillin was found be critically involved regulating development mesodermally derived structures...
The DiGeorge syndrome, the most common of microdeletion syndromes, affects multiple organs, including heart, nervous system, and kidney. It is caused by deletions on chromosome 22q11.2; genetic driver kidney defects unknown.
SHPS-1 is a receptor-like glycoprotein that undergoes tyrosine phosphorylation and binds SHP-2, an Src homology 2 domain containing protein phosphatase, in response to various mitogens. Cell adhesion extracellular matrix proteins such as fibronectin laminin also induced the of its association with SHP-2. These responses were markedly reduced cells overexpressing Csk kinase or lack focal family kinases Fyn. However, unlike Src, did not catalyze cytoplasmic vitro. Overexpression catalytically...
Members of the Src family tyrosine kinases function to phosphorylate focal adhesion (FA) proteins. To explore overlapping functions kinases, we have targeted Csk, a negative regulator family, FA structures. Expression FA-targeted Csk (FA-Csk) effectively reduced active form (nonphosphorylated at C-terminal regulatory tyrosine) members in cell. We found that fibroblasts expressing FA-Csk lost integrin-mediated adhesion. Activated (SrcY529F) as well activation putative signaling mediators...
Abstract A single topical application of 12‐ O ‐tetradecanoylphorbol‐13‐acetate (TPA) to mouse skin decreased 125 I‐labeled epidermal growth factor (EGF) binding in membrane preparations within 1 h while 1,8‐dihydroxy‐3‐methyl‐9‐anthrone (chrysarobin) gradually reduced with maximum inhibition at 15 h. Subsequently, I‐EGF increased ∼ 200% control from both TPA‐ and chrysarobin‐treated mice. TPA but not chrysarobin resulted a rapid translocation protein kinase C (PKC) the membrane; however,...
Significance Common deletions affecting multiple genes that cause birth defects can be studied by investigating each gene’s independent role in embryonic development. This study shows a specific gene, CRKL, which lies within the commonly deleted region at chromosome locus 22q11.2, is required for normal overall growth, and development of kidneys testes. Deletion only Crkl gene mice sufficient to increased incidence seen humans who possess deletion 22q11.2. CRKL one key whose contributes...
The adapter protein Crk-Like (CrkL) can associate with the Src substrate p130(Cas) (Cas). biological role of CrkL downstream Cas, however, has been largely obscure. Consistent ability to biochemically we found that triggers translocation focal adhesions (FAs) in a manner dependent on Cas. Forced localization CRKL FAs (FA-CRKL) by itself was sufficient induce activation Rac1 and Cdc42 rescued haptotaxis defects mouse embryonic fibroblasts (MEFs) lacking Src, Yes, Fyn, three broadly expressed...
Colony-stimulating factor-1 (CSF-1) induces expression of immediate early gene, such as c-myc and c-fos delayed genes D-type cyclins (D1 D2), whose products play essential roles in the G1 to S phase transition cell cycle. Little is known, however, about cytoplasmic signal transduction pathways that connect surface CSF-1 receptor these nucleus. We have investigated signaling mechanism CSF-1-induced D2 expression. Analyses autophosphorylation mutants show that, although certain individual...
CRKL (CRK-like) is an adapter protein predominantly phosphorylated in cells that express the tyrosine kinase p210(BCR-ABL), fusion product of a (9;22) chromosomal translocation causative for chronic myeloid leukemia. It has been unclear, however, whether plays functional role p210(BCR-ABL) transformation. Here, we show required to support interleukin-3-independent growth progenitor and long-term outgrowth B-lymphoid from fetal liver-derived hematopoietic cells. Furthermore, synthetic...
The adapter protein CRKL is required for the normal development of multiple tissues that rely on fibroblast growth factor 8 (FGF8). precise role in receptor signaling has been unclear, however. To address this issue, we first modeled three-dimensional structure by molecular dynamics. By taking advantage structural simulations, performed silico analysis interactions autophosphorylation sites FGR 1 (FGFR1) with SH2 domain or a highly related protein, CRK. As predicted confirm specific physical...
Background Raf Kinase Inhibitory Protein (RKIP, also PEBP1), a member of the Phosphatidylethanolamine Binding family, negatively regulates growth factor signaling by Raf/MAP kinase pathway. Since an organic compound, locostatin, was reported to bind RKIP and inhibit cell migration Raf-dependent mechanism, we addressed role in locostatin function. Methods/Findings We analyzed interaction with examined biological consequences binding on NMR studies show that precursor binds conserved...
To explore further the genetics of susceptibility skin tumor promotion in inbred mice, several aspects responsiveness to 12-O-etradecanoylphorbol-13-acetate (TPA) were examined C3H/He mice and segregating crosses between this mouse strain C57BL/6 as well BXD BXH recombinant (RI) strains. Dose-response relationships established for by TPA following initiation with 7, 12-dimethylbenz(a)anthracene B6C3F1, other stocks strains included comparison. The relative was: SENCAR > DBA/2 = B6D2F1 B6C3F1...
Abstract The oncoprotein c-Jun is a component of the activator protein-1 transcription factor complex, which involved in cellular proliferation, transformation, and death. stabilization critically important for its function. phosphorylation by NH2-terminal kinase 1 extracellular signal-regulated protein kinases reduces ubiquitination resulting increased c-Jun. In this report, we showed that COOH-terminal Src (CSK) binds with phosphorylates at Y26 Y170. Phosphorylation CSK, opposition to...
CRK and CRKL adapter proteins play essential roles in development cancer through their SRC homology 2 3 (SH2 SH3) domains. To gain insight into the origin of shared functions, we have investigated evolutionary history. We propose a term, crk/crkl ancestral (crka), for orthologs invertebrates before divergence vertebrate ancestor. isolated two expressed choanoflagellate Monosiga brevicollis, unicellular relative to metazoans. Consistent with its highly-conserved three-dimensional structure,...