Dynamin-dependent endocytosis of Bone Morphogenetic Protein2 (BMP2) and its receptors is dispensable for the initiation of Smad signaling.
The International Journal of Biochemistry & Cel... 76:51 (2016)
Bone Morphogenetic Protein (BMP) signal transduction via the canonical Smad158 pathway has previously been linked to dynamin-dependent endocytosis, since the application of chemical inhibitors of clathrin or dynamin in functional cell culture based assays negatively affects initiation and propag...
Differential regulation of translation and endocytosis of alternatively spliced forms of the type II bone morphogenetic protein (BMP) receptor.
Molecular Biology of the Cell 27(4):716 (2016)
The expression and function of transforming growth factor-β superfamily receptors are regulated by multiple molecular mechanisms. The type II BMP receptor (BMPRII) is expressed as two alternatively spliced forms, a long and a short form (BMPRII-LF and -SF, respectively), which differ by an ∼500 ...
TβRIII independently binds type I and type II TGF-β receptors to inhibit TGF-β signaling.
Molecular Biology of the Cell 26(19):3535 (2015)
Transforming growth factor-β (TGF-β) receptor oligomerization has important roles in signaling. Complex formation among type I and type II (TβRI and TβRII) TGF-β receptors is well characterized and is essential for signal transduction. However, studies on their interactions with the type III TGF...
Regulation of TGF-β receptor hetero-oligomerization and signaling by endoglin.
Molecular Biology of the Cell 26(17):3117 (2015)
Complex formation among transforming growth factor-β (TGF-β) receptors and its modulation by coreceptors represent an important level of regulation for TGF-β signaling. Oligomerization of ALK5 and the type II TGF-β receptor (TβRII) has been thoroughly investigated, both in vitro and in intact ce...
Rac-mediated Stimulation of Phospholipase Cγ2 Amplifies B Cell Receptor-induced Calcium Signaling.
Journal of Biological Chemistry 290(28):17056 (2015)
The Rho GTPase Rac is crucially involved in controlling multiple B cell functions, including those regulated by the B cell receptor (BCR) through increased cytosolic Ca(2+). The underlying molecular mechanisms and their relevance to the functions of intact B cells have thus far remained unknown....
Dab2 inhibits the cholesterol-dependent activation of JNK by TGF-β.
Molecular Biology of the Cell 25(10):1620 (2014)
Transforming growth factor-β (TGF-β) ligands activate Smad-mediated and noncanonical signaling pathways in a cell context-dependent manner. Localization of signaling receptors to distinct membrane domains is a potential source of signaling output diversity. The tumor suppressor/endocytic adaptor...
EGF receptor family: twisting targets for improved cancer therapies.
Growth Factors 32(2):74 (2014)
The epidermal growth factor receptor (EGFR) undergoes a conformational change in response to ligand binding. The ligand-induced changes in cell surface aggregation and mobility have a profound effect on the function of all the family members. Ligand also activates the EGFR intracellular kinase, ...
Src-mediated caveolin-1 phosphorylation affects the targeting of active Src to specific membrane sites.
Molecular Biology of the Cell 24(24):3881 (2013)
Src interactions with the plasma membrane are an important determinant of its activity. In turn, Src activity modulates its association with the membrane through binding of activated Src to phosphotyrosylated proteins. Caveolin-1 (Cav-1), a major component of caveolae, is a known Src phosphoryla...
Dual effects of Ral-activated pathways on p27 localization and TGF-β signaling.
Molecular Biology of the Cell 24(11):1812 (2013)
Constitutive activation or overactivation of Ras signaling pathways contributes to epithelial tumorigenesis in several ways, one of which is cytoplasmic mislocalization of the cyclin-dependent kinase inhibitor p27(Kip1) (p27). We previously showed that such an effect can be mediated by activatio...
The role of palmitoylation in regulating Ras localization and function.
Biochemical Society Transactions 41(1):79 (2013)
Ras GTPases are important regulators of pathways controlling proliferation, differentiation and transformation. Three ubiquitously expressed almost identical Ras genes are not functionally redundant; this has been attributed to their distinctive trafficking and localization profiles. A palmitoyl...
Differential effect of actomyosin relaxation on the dynamic properties of focal adhesion proteins.
PLoS ONE 8(9):e73549 (2013)
Treatment of cultured cells with inhibitors of actomyosin contractility induces rapid deterioration of stress fibers, and disassembly of the associated focal adhesions (FAs). In this study, we show that treatment with the Rho kinase inhibitor Y-27632, which blocks actomyosin contractility, induc...
Coated pit-mediated endocytosis of the type I transforming growth factor-β (TGF-β) receptor depends on a di-leucine family signal and is not required for signaling.
Journal of Biological Chemistry 287(32):26876 (2012)
The roles of transforming growth factor-β (TGF-β) receptor endocytosis in signaling have been investigated in numerous studies, mainly through the use of endocytosis inhibitory treatments, yielding conflicting results. Two potential sources for these discrepancies were the pleiotropic effects of...
Oligomeric interactions of TGF-β and BMP receptors.
FEBS Letters 586(14):1885 (2012)
Transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP) cytokines participate in a multiplicity of ways in the regulation of numerous physiological and pathological processes. Their wide-ranging biological functions are controlled by several mechanisms, including regulation of ...
Role for TBC1D20 and Rab1 in hepatitis C virus replication via interaction with lipid droplet-bound nonstructural protein 5A.
Journal of Virology 86(12):6491 (2012)
Replication and assembly of hepatitis C virus (HCV) depend on the host's secretory and lipid-biosynthetic machinery. Viral replication occurs on endoplasmic reticulum (ER)-derived modified membranes, while viral assembly is thought to occur on lipid droplets (LDs). A physical association and coo...
Accurate quantification of diffusion and binding kinetics of non-integral membrane proteins by FRAP.
Traffic 12(11):1648 (2011)
Non-integral membrane proteins frequently act as transduction hubs in vital signaling pathways initiated at the plasma membrane (PM). Their biological activity depends on dynamic interactions with the PM, which are governed by their lateral and cytoplasmic diffusion and membrane binding/unbindin...
Raft protein clustering alters N-Ras membrane interactions and activation pattern.
Molecular and Cellular Biology 31(19):3938 (2011)
The trafficking, membrane localization, and lipid raft association of Ras proteins, which are crucial oncogenic mediators, dictate their isoform-specific biological responses. Accordingly, their spatiotemporal dynamics are tightly regulated. While extensively studied for H- and K-Ras, such infor...
How prenylation and S-acylation regulate subcellular targeting and function of ROP GTPases.
Plant Signaling & Behavior 6(7):1026 (2011)
Rho of Plants (ROP) small G proteins function at discrete domains of the plasma and possibly endo membranes. ROPs are synthesized as soluble proteins and their attachment to membranes and partitioning in membrane microdomains are facilitated by the posttranslational lipid modifications prenylati...
Formation of stable homomeric and transient heteromeric bone morphogenetic protein (BMP) receptor complexes regulates Smad protein signaling.
Journal of Biological Chemistry 286(22):19287 (2011)
The type I and type II bone morphogenetic protein receptors (BMPRI and BMPRII) are present at the plasma membrane as monomers and homomeric and heteromeric complexes, which are modulated by ligand binding. The complexes of their extracellular domains with ligand were shown to form heterotetramer...
Actomyosin-generated tension controls the molecular kinetics of focal adhesions.
Journal of Cell Science 124(Pt 9):1425 (2011)
Focal adhesions (FAs) have key roles in the interaction of cells with the extracellular matrix (ECM) and in adhesion-mediated signaling. These dynamic, multi-protein structures sense the ECM both chemically and physically, and respond to external and internal forces by changing their size and si...
Differential effects of prenylation and s-acylation on type I and II ROPS membrane interaction and function.
Plant Physiology 155(2):706 (2011)
Prenylation primarily by geranylgeranylation is required for membrane attachment and function of type I Rho of Plants (ROPs) and Gγ proteins, while type II ROPs are attached to the plasma membrane by S-acylation. Yet, it is not known how prenylation affects ROP membrane interaction dynamics and ...