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  • phosphatases
  • Although Csk itself may not be mutated in human cancers, perturbation of the regulatory system consisting of Csk, Cbp/PAG1, or other scaffolds, and certain tyrosine phosphatases may explain the upregulation of SFKs frequently observed in human cancers. (ijbs.com)
  • Tim-3 contains no known motifs for the recruitment of inhibitory phosphatases, but it may actually increase signaling downstream of TCR/CD3, at least under acute conditions. (jimmunol.org)
  • lipid rafts
  • The primary structure can be divided into five functional domains (Fig. 1 A). The N-terminal domain contains signals for lipid modification: myristoylation (in all SFKs) and palmitoylation (in all but c-Src and Blk) signals, both of which are required for membrane association of SFKs (Fig. 1 B). Palmitoylation has been implicated in the stable localization of SFKs in membrane microdomains called "lipid rafts" [ 14 ]. (ijbs.com)
  • As CD2 physically interacts with both Lck and Fyn, preferentially inside lipid rafts, and reflecting the increase of CD2 in lipid rafts following activation, CD2 can mediate the interaction between the two kinases and the consequent boost in kinase activity in lipid rafts. (jimmunol.org)
  • endocytosis
  • These data provide further evidence of a relationship between receptor-mediated signalling and endocytosis, and disclose a novel functional role for Cbl in HGF receptor signalling. (nih.gov)
  • Furthermore, RICH-1 exhibits a BIN/amphiphysin/Rvsp (BAR) domain which associates with membrane lipids, and in addition this domain was shown to deform liposomes in an in vitro assay, which is thought to mimic the deformation of cellular lipid bilayers, for example the invagination of the plasma membrane during endocytosis. (diva-portal.org)
  • 1 - 3 The actin filament system also contributes to development by regulating endocytosis, a fundamental process that is essential to downregulate or attenuate extracellular signaling, to shape morphogen gradients and to orchestrate cell fate decisions within a tissue. (pubmedcentralcanada.ca)
  • During endocytosis, actin generates the force that (1) drives membrane invagination, (2) helps to constrict the neck of a nascent vesicle, (3) aids the subsequent scission of the vesicle and (4) propels the vesicle away from the plasma membrane. (pubmedcentralcanada.ca)
  • vitro
  • Leptin also induced mRNA expression of the JAK-STAT inhibitor suppressor of cytokine signaling (SOCS)3 in INS-1 β-cells and human pancreatic islets in vitro and in pancreatic islets of ob/ob mice in vivo. (diabetesjournals.org)
  • However, the stoichiometry of this interaction is very low and is only detectable by in vitro kinase assays ( 8 ). (jimmunol.org)
  • expression
  • The diphtheria toxin repressor (DtxR) regulates the expression of several iron-sensitive genes in Corynebacterium diphtheriae , including the iron-response protein genes ( irp ), a heme oxygenase, and the diphtheria toxin gene ( tox ) ( 1 - 3 ). (pnas.org)
  • Leptin has also been shown to inhibit insulin secretion and preproinsulin gene expression in pancreatic β-cells ( 3 - 6 ), thereby establishing an adipoinsular feedback loop in concert with stimulatory action of insulin on leptin secretion from the adipose tissue ( 7 , 8 ). (diabetesjournals.org)
  • Expression of a p85α mutant lacking the p110-binding site (Δp85) also inhibited phosphotyrosine-associated PI 3-kinase activity but not p110-associated activity. (asm.org)
  • Expression increases quickly after induction of adipocyte differentiation, reaches a maximum after 3 hours and decreases by 12 hours. (merckmillipore.com)
  • Biochemical analysis comparing stimulated naive and primed TCR-transgenic cells revealed no obvious differences in expression of total CTLA-4, tyrosine-phosphorylated CTLA-4, and associated Src homology domain 2-containing protein tyrosine phosphatase. (jimmunol.org)
  • These patterns of expression demonstrate how a single protein-tyrosine kinase might play diverse roles at different times during development. (sdbonline.org)
  • 12 In addition, there is evidence that multiple domains in the HIF protein regulate its expression and that they do so by altering the ubiquitination of HIF-1α under nonhypoxic conditions. (ahajournals.org)
  • proline-rich
  • Binding of the proline-rich peptide by the C-terminal domain of DtxR presents an example of peptide binding by a prokaryotic Src homology 3-like protein. (pnas.org)
  • We also present evidence that this prokaryotic SH3-like domain binds to a proline-rich segment that is located in the region linking the N- and C-terminal domains of DtxR and is conserved in all known DtxR homologues. (pnas.org)
  • p85α and p85β belong to the full-length version of the regulatory subunits and consist of an SH3 domain, a Bcr homology domain flanked by two proline-rich domains, an N-terminal SH2 (nSH2) domain, an inter-SH2 (iSH2) region containing the p110-binding site, and a C-terminal SH2 (cSH2) domain ( 27 ). (asm.org)
  • Cell surface receptor signaling - The two GRB2 SH3 domains bind to the proline-rich regions of the guanine nucleotide releasing factor son of sevenless (SOS-1) protein, and the GRB2-SOS-1 complex preexists in the cytoplasm of resting cells. (atlasgeneticsoncology.org)
  • plasma membrane
  • Tyrosine kinases, which exist only in animals, play important roles in controlling animal-specific cellular functions such as rapid cell-cell communication via the plasma membrane [ 1 , 2 ]. (ijbs.com)
  • In many mitogenic signaling pathways, recruitment of GRB2 from the cytosol, where it is already bound to the guanine nucleotide exchange factor SOS-1 via its amino-terminal SH3 domain, brings SOS1 in close proximity to Ras at the plasma membrane. (atlasgeneticsoncology.org)
  • actin
  • Among the tyrosine kinases, c-Abl and its relative Arg are unique in binding directly to F-actin. (biologists.org)
  • On the molecular level, the Arp2/3 complex might provide the driving force for formation of membrane protrusions by nucleating actin polymerization from the sides of existing filaments. (biologists.org)
  • intramolecular interactions
  • This stems from the constant competition between self-inhibitory intramolecular interactions (mostly via the SH3 and SH2 domains) and generally activating intermolecular interactions with ligands. (springer.com)
  • Leucine 255 of Src couples intramolecular interactions to inhibition of catalysis. (springer.com)
  • MAPK
  • The role of the MAPK (Mitogen-activated protein kinase) signal pathway in neuronal development has received increasing attention in the past several years. (wm.edu)
  • pathways
  • These form stable homodimers that are secreted in both constitutive and regulated pathways ( 41 ) and that represent high-affinity ligands for the Trk receptor kinases ( 4 ). (physiology.org)
  • We suggest that Tim-3 may contribute to T cell exhaustion by enhancing TCR-signaling pathways. (jimmunol.org)
  • activation
  • On the other hand, the controlled activation of Abl kinases is required for a large number of normal cellular processes. (springer.com)
  • CTLA-4 is an alternative counter-receptor for CD80 and CD86 that is expressed on T cells only after activation and binds these ligands with higher avidity than does CD28 ( 3 , 4 ). (jimmunol.org)
  • B) Amino acid alignments of N-terminal unique domain, activation loop and C-terminal regulatory tail in SFKs. (ijbs.com)
  • Our data indicate that the cation channel-kinase "association" requires src homology 3 (SH3) domain protein-protein interactions, and that disruption of this interaction prevents channel modulation and attenuates the long-lasting depolarization produced by cation channel activation. (jneurosci.org)
  • structurally
  • The N-terminal domain is structurally well-defined and is responsible for Fe 2+ binding, dimerization, and DNA binding. (pnas.org)
  • amino
  • Many well represented domains recognize and bind to primary sequences less than 10 amino acids in length called Short Linear Motifs (SLiMs). (biomedcentral.com)
  • phosphotyrosine
  • Increasing the level of p85α or AS53, but not p50α, inhibited both phosphotyrosine-associated and p110-associated PI 3-kinase activities. (asm.org)
  • roles
  • A significant advance came when peptide-library methods were developed to identify sequences recognized by SH2 domains, which is a globular domain that plays important roles in cellular signal transduction. (biomedcentral.com)
  • Mayer BJ, Baltimore D. Mutagenic analysis of the roles of SH2 and SH3 domains in regulation of the Abl tyrosine kinase. (springer.com)