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SH3 receptors and co-factors

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https://www.readbyqxmd.com/read/27620165/vasodilator-stimulated-phosphoprotein-vasp-dependent-and-independent-pathways-regulate-thrombin-induced-activation-of-rap1b-in-platelets
#1
Peter M Benz, Hebatullah Laban, Joana Zink, Lea Günther, Ulrich Walter, Stepan Gambaryan, Karim Dib
BACKGROUND: Vasodilator-Stimulated Phosphoprotein (VASP) is involved in the inhibition of agonist-induced platelet aggregation by cyclic nucleotides and the adhesion of platelets to the vascular wall. αIIbβ3 is the main integrin responsible for platelet activation and Rap1b plays a key role in integrin signalling. We investigated whether VASP is involved in the regulation of Rap1b in platelets since VASP-null platelets exhibit augmented adhesion to endothelial cells in vivo. METHODS: Washed platelets from wild type and VASP-deficient mice were stimulated with thrombin, the purinergic receptors agonist ADP, or the thromboxane A2 receptor agonist U46619 and Rap1b activation was measured using the GST-RalGDS-RBD binding assay...
2016: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/26286913/sh3bgrl3-protein-as-a-potential-prognostic-biomarker-for-urothelial-carcinoma-a-novel-binding-partner-of-epidermal-growth-factor-receptor
#2
Cheng-Yao Chiang, Chin-Chen Pan, Hong-Yi Chang, Ming-Derg Lai, Tzong-Shin Tzai, Yuh-Shyan Tsai, Pin Ling, Hsiao-Sheng Liu, Bi-Fang Lee, Hong-Ling Cheng, Chung-Liang Ho, Shu-Hui Chen, Nan-Haw Chow
PURPOSE: Mass spectrometry-based biomarker discovery has clinical benefit. To identify novel biomarkers for urothelial carcinoma, we performed quantitative proteomics on pooled urine pairs from patients with and without urothelial carcinoma. EXPERIMENTAL DESIGN: Shot-gun proteomics using liquid chromatography-tandem mass spectrometry and stable isotope dimethyl labeling identified 219 candidate proteins. The potential implication of SH3 domain binding glutamic acid-rich protein like 3 (SH3BGRL3) was examined by immunoblotting of the urine (n = 13) and urothelial tumors (n = 32)...
December 15, 2015: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/23589285/kr%C3%A3-ppel-like-factor-11-regulates-the-expression-of-metabolic-genes-via-an-evolutionarily-conserved-protein-interaction-domain-functionally-disrupted-in-maturity-onset-diabetes-of-the-young
#3
Gwen Lomberk, Adrienne Grzenda, Angela Mathison, Carlos Escande, Jin-San Zhang, Ezequiel Calvo, Laurence J Miller, Juan Iovanna, Eduardo N Chini, Martin E Fernandez-Zapico, Raul Urrutia
The function of Krüppel-like factor 11 (KLF11) in the regulation of metabolic pathways is conserved from flies to human. Alterations in KLF11 function result in maturity onset diabetes of the young 7 (MODY7) and neonatal diabetes; however, the mechanisms underlying the role of this protein in metabolic disorders remain unclear. Here, we investigated how the A347S genetic variant, present in MODY7 patients, modulates KLF11 transcriptional activity. A347S affects a previously identified transcriptional regulatory domain 3 (TRD3) for which co-regulators remain unknown...
June 14, 2013: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/22952966/cortactin-is-a-substrate-of-activated-cdc42-associated-kinase-1-ack1-during-ligand-induced-epidermal-growth-factor-receptor-downregulation
#4
Laura C Kelley, Scott A Weed
BACKGROUND: Epidermal growth factor receptor (EGFR) internalization following ligand binding controls EGFR downstream pathway signaling activity. Internalized EGFR is poly-ubiquitinated by Cbl to promote lysosome-mediated degradation and signal downregulation. ACK1 is a non-receptor tyrosine kinase that interacts with ubiquitinated EGFR to facilitate EGFR degradation. Dynamic reorganization of the cortical actin cytoskeleton controlled by the actin related protein (Arp)2/3 complex is important in regulating EGFR endocytosis and vesicle trafficking...
2012: PloS One
https://www.readbyqxmd.com/read/22366926/the-p85%C3%AE-regulatory-subunit-of-pi3k-mediates-camp-pka-and-retinoic-acid-biological-effects-on-mcf7-cell-growth-and-migration
#5
Caterina F Donini, Erika Di Zazzo, Candida Zuchegna, Marina Di Domenico, Sonia D'Inzeo, Arianna Nicolussi, Enrico V Avvedimento, Anna Coppa, Antonio Porcellini
Phosphoinositide-3-OH kinase (PI3K) signalling regulates various cellular processes, including cell survival, growth, proliferation and motility, and is among the most frequently mutated pathways in cancer. Although the involvement of p85αPI3K SH2 domain in signal transduction has been extensively studied, the function of the SH3 domain at the N-terminus remains elusive. A serine (at codon 83) adjacent to the N-terminal SH3 domain in the PI3K regulatory subunit p85αPI3K that is phosphorylated by protein kinase A (PKA) in vivo and in vitro has been identified...
May 2012: International Journal of Oncology
https://www.readbyqxmd.com/read/21540179/differential-regulation-of-the-postsynaptic-clustering-of-%C3%AE-aminobutyric-acid-type-a-gabaa-receptors-by-collybistin-isoforms
#6
Tzu-Ting Chiou, Bevan Bonhomme, Hongbing Jin, Celia P Miralles, Haiyan Xiao, Zhanyan Fu, Robert J Harvey, Kirsten Harvey, Stefano Vicini, Angel L De Blas
Collybistin promotes submembrane clustering of gephyrin and is essential for the postsynaptic localization of gephyrin and γ-aminobutyric acid type A (GABA(A)) receptors at GABAergic synapses in hippocampus and amygdala. Four collybistin isoforms are expressed in brain neurons; CB2 and CB3 differ in the C terminus and occur with and without the Src homology 3 (SH3) domain. We have found that in transfected hippocampal neurons, all collybistin isoforms (CB2(SH3+), CB2(SH3-), CB3(SH3+), and CB3(SH3-)) target to and concentrate at GABAergic postsynapses...
June 24, 2011: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/21309750/the-cdc42-associated-kinase-ack1-is-not-autoinhibited-but-requires-src-for-activation
#7
Wing Chan, Soon-Tuck Sit, Ed Manser
The non-RTK (receptor tyrosine kinase) ACK1 [activated Cdc42 (cell division cycle 42)-associated kinase 1] binds a number of RTKs and is associated with their endocytosis and turnover. Its mode of activation is not well established, but models have suggested that this is an autoinhibited kinase. Point mutations in its SH3 (Src homology 3)- or EGF (epidermal growth factor)-binding domains have been reported to activate ACK1, but we find neither of the corresponding W424K or F820A mutations do so. Indeed, deletion of the various ACK1 domains C-terminal to the catalytic domain are not associated with increased activity...
April 15, 2011: Biochemical Journal
https://www.readbyqxmd.com/read/21081186/the-interactome-of-a-ptb-domain-containing-adapter-protein-odin-revealed-by-silac
#8
Jun Zhong, Raghothama Chaerkady, Kumaran Kandasamy, Marjan Gucek, Robert N Cole, Akhilesh Pandey
Signal transduction pathways are tightly controlled by positive and negative regulators. We have previously identified Odin (also known as ankyrin repeat and sterile alpha motif domain-containing 1A; gene symbol ANKS1A) as a negative regulator of growth factor signaling; however, the mechanisms through which Odin regulates these pathways remain to be elucidated. To determine how Odin negatively regulates growth factor signaling, we undertook a proteomic approach to systematically identify proteins that interact with Odin using the SILAC strategy...
March 1, 2011: Journal of Proteomics
https://www.readbyqxmd.com/read/20622020/complex-role-of-collybistin-and-gephyrin-in-gabaa-receptor-clustering
#9
Leila Saiepour, Celine Fuchs, Annarita Patrizi, Marco Sassoè-Pognetto, Robert J Harvey, Kirsten Harvey
Gephyrin and collybistin are key components of GABA(A) receptor (GABA(A)R) clustering. Nonetheless, resolving the molecular interactions between the plethora of GABA(A)R subunits and these clustering proteins is a significant challenge. We report a direct interaction of GABA(A)R α2 and α3 subunit intracellular M3-M4 domain (but not α1, α4, α5, α6, β1-3, or γ1-3) with gephyrin. Curiously, GABA(A)R α2, but not α3, binds to both gephyrin and collybistin using overlapping sites. The reciprocal binding sites on gephyrin for collybistin and GABA(A)R α2 also overlap at the start of the gephyrin E domain...
September 17, 2010: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/20603213/the-sh2-domain-protein-shep1-regulates-the-in-vivo-signaling-function-of-the-scaffolding-protein-cas
#10
Séverine Roselli, Yann Wallez, Lei Wang, Virginie Vervoort, Elena B Pasquale
The members of the p130Cas (Cas) family are important scaffolding proteins that orchestrate cell adhesion, migration and invasiveness downstream of integrin adhesion receptors and receptor tyrosine kinases by recruiting enzymes and structural molecules. Shep1, BCAR3/AND-34 and NSP1 define a recently identified family of SH2 domain-containing proteins that constitutively bind Cas proteins through a Cdc25-type nucleotide exchange factor-like domain. To gain insight into the functional interplay between Shep1 and Cas in vivo, we have inactivated the Shep1 gene in the mouse through Cre-mediated deletion of the exon encoding the SH2 domain...
November 2010: Cellular Signalling
https://www.readbyqxmd.com/read/20554524/ptk6-inhibits-down-regulation-of-egf-receptor-through-phosphorylation-of-arap1
#11
Shin-Ae Kang, Eun-Saem Lee, Hye-Young Yoon, Paul A Randazzo, Seung-Taek Lee
PTK6 (also known as Brk) is a non-receptor-tyrosine kinase containing SH3, SH2, and catalytic domains, that is expressed in more than 60% of breast carcinomas but not in normal mammary tissues. To analyze PTK6-interacting proteins, we have expressed Flag-tagged PTK6 in HEK293 cells and performed co-immunoprecipitation assays with Flag antibody-conjugated agarose. A 164-kDa protein in the precipitated fraction was identified as ARAP1 (also known as centaurin delta-2) by MALDI-TOF mass analysis. ARAP1 associated with PTK6 in an EGF/EGF receptor (EGFR)-dependent manner...
August 20, 2010: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/20451654/activation-of-erk-by-sonic-hedgehog-independent-of-canonical-hedgehog-signalling
#12
Hong Chang, Qing Li, Ricardo C Moraes, Michael T Lewis, Paul A Hamel
Hedgehog (Hh) signalling is mediated through the Patched-1 (Ptch1) receptor. Hh-binding to Ptch1 blocks the inhibitory effects of Ptch1 on the activity of the transmembrane protein, Smoothened (Smo), resulting induction of target genes by the Gli-family of transcription factors. We demonstrate here that Hh-binding to Ptch1 stimulates activation of Erk1/2. This activation is insensitive to the small molecule Smo antagonists and occurs in a cell line that does not express Smo. Specifically, the C-terminus of Ptch1 harbours motifs encoding Class I and II SH3-binding sites...
September 2010: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/20404345/rac1-recruits-the-adapter-protein-cms-cd2ap-to-cell-cell-contacts
#13
Trynette J van Duijn, Eloise C Anthony, Paul J Hensbergen, André M Deelder, Peter L Hordijk
Rac1 is a member of the Rho family of small GTPases, which regulate cell adhesion and migration through their control of the actin cytoskeleton. Rho-GTPases are structurally very similar, with the exception of a hypervariable domain in the C terminus. Using peptide-based pulldown assays in combination with mass spectrometry, we previously showed that the hypervariable domain in Rac1 mediates specific protein-protein interactions. Most recently, we found that the Rac1 C terminus associates to the ubiquitously expressed adapter protein CMS/CD2AP...
June 25, 2010: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/19439179/brk-phosphorylates-psf-promoting-its-cytoplasmic-localization-and-cell-cycle-arrest
#14
Kiven E Lukong, Marc-Etienne Huot, Stéphane Richard
BReast tumor Kinase (BRK) also known as protein kinase 6 (PTK6) is a non-receptor tyrosine kinase overexpressed in the majority of human breast carcinoma. The expression of BRK is a known prognostic marker of breast carcinoma. BRK has been shown to lie downstream of epidermal growth factor (EGF) signaling and mediate effects on cell proliferation and migration. To identify BRK substrates and interacting proteins, we undertook a proteomic approach. BRK immune complexes were purified from the BT-20 breast cancer cell line and analyzed by mass spectrometry...
September 2009: Cellular Signalling
https://www.readbyqxmd.com/read/18985015/multi-transmembrane-protein-k15-of-kaposi-s-sarcoma-associated-herpesvirus-targets-lyn-kinase-in-the-membrane-raft-and-induces-nfat-ap1-activities
#15
Nam-Hyuk Cho, Young-Ki Choi, Joong-Kook Choi
Viral proteins of gamma-2 herpesviruses, such as LMP2A of Epstein Barr virus (EBV) and Tip of herpesvirus saimiri (HVS) dysregulate lymphocyte signaling by interacting with Src family kinases. K15 open reading frame of Kaposi's sarcoma associated herpesvirus (KSHV), located at the right end of the viral genome, encodes several splicing variants differing in numbers of transmembrane domains. Previously, we demonstrated that the cytoplasmic tail of the K15 protein interfered with B cell receptor signal transduction to cellular tyrosine phosphorylation and calcium mobilization...
October 31, 2008: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/18707241/the-proline-rich-region-of-hiv-1-nef-affects-cxcr4-mediated-chemotaxis-in-jurkat-t-cells
#16
Carol Man Yuk Lee, Salvador Gala, Graeme John Stewart, Peter Williamson
T-cell chemotaxis constitutes an essential function of the immune response, since active secretion of chemokines controls homing and recruitment of leukocytes into tissues. Modification of chemotactic responses by HIV-1 may provide a mechanism to increase viral spread, and may be an important factor in HIV-1 disease progression and pathogenesis. One potent T-cell chemoattractant is SDF-1 alpha, the natural ligand for the HIV-1 co-receptor CXCR4. In addition, the HIV-1 gp120 molecule shares the chemotactic properties of several chemokines, including SDF-1 alpha...
September 2008: Viral Immunology
https://www.readbyqxmd.com/read/18647389/the-central-proline-rich-region-of-pob1-reps2-plays-a-regulatory-role-in-epidermal-growth-factor-receptor-endocytosis-by-binding-to-14-3-3-and-sh3-domain-containing-proteins
#17
Laura Tomassi, Anna Costantini, Salvatore Corallino, Elena Santonico, Martina Carducci, Gianni Cesareni, Luisa Castagnoli
BACKGROUND: The human POB1/REPS2 (Partner of RalBP1) protein is highly conserved in mammals where it has been suggested to function as a molecular scaffold recruiting proteins involved in vesicular traffic and linking them to the actin cytoskeleton remodeling machinery. More recently POB1/REPS2 was found highly expressed in androgen-dependent prostate cancer cell lines, while one of its isoforms (isoform 2) is down regulated during prostate cancer progression. RESULTS: In this report we characterize the central proline rich domain of POB1/REPS2 and we describe for the first time its functional role in receptor endocytosis...
2008: BMC Biochemistry
https://www.readbyqxmd.com/read/18602463/ataxin-2-associates-with-the-endocytosis-complex-and-affects-egf-receptor-trafficking
#18
David Nonis, Mirko H H Schmidt, Simone van de Loo, Florian Eich, Ivan Dikic, Joachim Nowock, Georg Auburger
Ataxin-2 is a novel protein, where the unstable expansion of an internal polyglutamine domain can cause the neurodegenerative disease Spinocerebellar Ataxia type 2 (SCA2). To elucidate its cellular function, we have used full-length ataxin-2 as bait in a yeast two-hybrid screen of human adult brain cDNA. As binding partners we found endophilin A1 and A3, two brain-expressed members of the endophilin A family involved in synaptic vesicle endocytosis. Co-immunoprecipitation studies confirmed the binding of these proteins as an endogenous complex in mouse brain...
October 2008: Cellular Signalling
https://www.readbyqxmd.com/read/18021396/human-ncu-g1-can-function-as-a-transcription-factor-and-as-a-nuclear-receptor-co-activator
#19
Knut R Steffensen, Mariam Bouzga, Frode Skjeldal, Cecilie Kasi, Almira Karahasan, Vilborg Matre, Oddmund Bakke, Sylvain Guérin, Winnie Eskild
BACKGROUND: Novel, uncharacterised proteins represent a challenge in biochemistry and molecular biology. In this report we present an initial functional characterization of human kidney predominant protein, NCU-G1. RESULTS: NCU-G1 was found to be a highly conserved nuclear protein rich in proline with a molecular weight of approximately 44 kDa. It is localized on chromosome 1 and consists of 6 exons. Analysis of the amino acid sequence revealed no known transcription activation domains or DNA binding regions, however, four nuclear receptor boxes (LXXLL), and four SH3-interaction motives in addition to numerous potential phosphorylation sites were found...
2007: BMC Molecular Biology
https://www.readbyqxmd.com/read/17537434/palladin-interacts-with-sh3-domains-of-spin90-and-src-and-is-required-for-src-induced-cytoskeletal-remodeling
#20
Mikko Rönty, Anu Taivainen, Leena Heiska, Carol Otey, Elisabeth Ehler, Woo Keun Song, Olli Carpen
Palladin and SPIN90 are widely expressed proteins, which participate in modulation of actin cytoskeleton by binding to a variety of scaffold and signaling molecules. Cytoskeletal reorganization can be induced by activation of signaling pathways, including the PDGF receptor and Src tyrosine kinase pathways. In this study we have analyzed the interplay between palladin, SPIN90 and Src and characterized the role of palladin and SPIN90 in PDGF and Src-induced cytoskeletal remodeling. We show that the SH3 domains of SPIN90 and Src directly bind palladin's poly-proline sequence and the interaction controls intracellular targeting of SPIN90...
July 15, 2007: Experimental Cell Research
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