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1.
Role of Sam68 as an adaptor protein in signal transduction 总被引:3,自引:0,他引:3
Najib S Martín-Romero C González-Yanes C Sánchez-Margalet V 《Cellular and molecular life sciences : CMLS》2005,62(1):36-43
Sam68, the substrate of Src in mitosis, belongs to the family of RNA binding proteins. Sam68 contains consensus sequences to interact with other proteins via specific domains. Thus, Sam68 has various proline-rich sequences to interact with SH3 domain-containing proteins. Moreover, Sam68 also has a C-terminal domain rich in tyrosine residues that is a substrate for tyrosine kinases. Tyrosine phosphorylation of Sam68 promotes its interaction with SH2 containing proteins. The association of Sam68 with SH3 domain-containing proteins, and its tyrosine phosphorylation may negatively regulate its RNA binding activity. The presence of these consensus sequences to interact with different domains allows this protein to participate in signal transduction pathways triggered by tyrosine kinases. Thus, Sam68 participates in the signaling of T cell receptors, leptin and insulin receptors. In these systems Sam68 is tyrosine phosphorylated and recruited to specific signaling complexes. The participation of Sam68 in signaling suggests that it may function as an adaptor molecule, working as a dock to recruit other signaling molecules. Finally, the connection between this role of Sam68 in protein-protein interaction with RNA binding activity may connect signal transduction of tyrosine kinases with the regulation of RNA metabolism.Received 16 July 2004; received after revision 12 August 2004; accepted 18 August 2004 相似文献
2.
The suppressors of cytokine signalling (SOCS) 总被引:10,自引:0,他引:10
3.
Llorca O 《Cellular and molecular life sciences : CMLS》2008,65(9):1302-1310
In mammals, the mannose receptor family consists of four members, Endo180, DEC-205, phospholipase A2 receptor and the mannose receptor. The extracellular domains of all these receptors contain a similar arrangement of domains
in which an Nterminal cysteine-rich domain is followed by a single fibronectin type II domain and eight or ten C-type lectin-like
domains. This review focuses on the threedimensional structure of the receptors in the mannose receptor family and its functional
implication. Recent research has revealed that several members of this family can exist in at least two configurations: an
extended conformation with the N-terminal cysteinerich domain pointing outwards from the cell membrane and a bent conformation
where the N-terminal domains fold back to interact with C-type lectin-like domains at the middle of the structure. Conformational
transitions between these two states seem to regulate the interaction of these receptors with ligands and their oligomerization.
Received 25 October 2007; received after revision 23 November 2007; accepted 7 December 2007 相似文献
4.
5.
Kertész A Váradi G Tóth GK Fajka-Boja R Monostori E Sármay G 《Cellular and molecular life sciences : CMLS》2006,63(22):2682-2693
Phosphopeptides interacting with src homology 2 (SH2) domains can activate essential signaling enzymes in vitro. When delivered to cells, they may disrupt protein-protein interactions, thereby influencing intracellular signaling. We
showed earlier that phosphopeptides corresponding to the inhibitory motif of Fcγ receptor IIb and a motif of the Grb2-associated
binder 1 adaptor protein activate SH2-containing tyrosine phosphatase 2 in vitro. To study the ex vivo effects of these peptides, we have now compared different methods for peptide delivery: (i) permeabilization of the target
cells and (ii) the use of cell-permeable vectors, which are potentially able to transport biologically active compounds into
B cells. We found octanoyl-Arg8 to be an optimal carrier for the delivery of phosphopeptides to the cells. With this strategy, the function of cell-permeable
SHP-2-binding phosphopeptides was analyzed. These peptides modulated the protein phosphorylation in B cells in a dose- and
time-dependent manner.
Received 27 July 2006; received after revision 4 September 2006; accepted 18 September 2006 相似文献
6.
Immunophilins: for the love of proteins 总被引:1,自引:0,他引:1
Barik S 《Cellular and molecular life sciences : CMLS》2006,63(24):2889-2900
Immunophilins are chaperones that may also exhibit peptidylprolyl isomerase (PPIase) activity. This review summarizes our
knowledge of the two largest families of immunophilins, namely cyclophilin and FK506-binding protein, and a novel chimeric
dual-family immunophilin, named FK506- and cyclosporin-binding protein (FCBP). The larger members of each family are modular
in nature, consisting of multiple PPIase and/or protein-protein interaction domains. Despite the apparent difference in their
sequence and three-dimensional structure, the three families encode similar enzymatic and biological functions. Recent studies
have revealed that many immunophilins possess a chaperone function independent of PPIase activity. Knockout animal studies
have confirmed multiple essential roles of immunophilins in physiology and development. An immunophilin is indeed a natural
‘protein-philin’ (Greek ‘philin’ = friend) that interacts with proteins to guide their proper folding and assembly.
Received: 7 May 2006; received after revision 3 July 2006; accepted 24 August 2006 相似文献
7.
The BAG (Bcl-2 associated athanogene) family is a multifunctional group of proteins that perform diverse functions ranging from apoptosis to tumorigenesis.
An evolutionarily conserved group, these proteins are distinguished by a common conserved region known as the BAG domain.
BAG genes have been found in yeasts, plants, and animals, and are believed to function as adapter proteins forming complexes
with signaling molecules and molecular chaperones. In humans, a role for BAG proteins has been suggested in carcinogenesis,
HIV infection, and Parkinson’s disease. These proteins are therefore potential therapeutic targets, and their expression in
cells may serve as a predictive tool for such diseases. In plants, the Arabidopsis thaliana genome contains seven homologs of the BAG family, including four with domain organization similar to animal BAGs. Three members
contain a calmodulin-binding domain possibly reflecting differences between plant and animal programmed cell death. This review
summarizes current understanding of BAG proteins in both animals and plants.
Received 21 November 2007; received after revision 17 December 2007; accepted 2 January 2008 相似文献
8.
T. Jenuwein G. Laible R. Dorn G. Reuter 《Cellular and molecular life sciences : CMLS》1998,54(1):80-93
The SET domain is a 130-amino acid, evolutionarily conserved sequence motif present in chromosomal proteins that function
in modulating gene activities from yeast to mammals. Initially identified as members of the Polycomb- and trithorax-group (Pc-G and trx-G) gene families, which are required to maintain expression boundaries of homeotic selector (HOM-C) genes,
SET domain proteins are also involved in position-effect-variegation (PEV), telomeric and centromeric gene silencing, and
possibly in determining chromosome architecture. These observations implicate SET domain proteins as multifunctional chromatin
regulators with activities in both eu- and heterochromatin – a role consistent with their modular structure, which combines
the SET domain with additional sequence motifs of either a cysteine-rich region/zinc-finger type or the chromo domain. Multiple
functions for chromatin regulators are not restricted to the SET protein family, since many trx-G (but only very few Pc-G)
genes are also modifiers of PEV. Together, these data establish a model in which the modulation of chromatin domains is mechanistically
linked with the regulation of key developmental loci (e.g. HOM-C). 相似文献
9.
A. Hamadi T. B. Deramaudt K. Takeda P. Rondé 《Cellular and molecular life sciences : CMLS》2009,66(2):324-338
Cell migration requires the coordinated turnover of focal adhesions, a process that involves FAK phosphorylation. Since Src
is the major kinase implicated in FAK phosphorylation, we focus here on the role of Src activation on adhesion remodelling.
In astrocytoma cells, constitutively activated Src induces both FAK phosphorylation and adhesion rearrangement. To evaluate
how Src controls these processes, we used a recently described Src reporter to monitor the dynamics of Src phosphorylation.
Upon Src activation, focal adhesions started to disassemble while Src appeared highly expressed at newly formed membrane ruffles.
Kinetic analysis of time-lapse movies showed that loss of phospho-Src at focal adhesions was time-correlated with the appearance
of membrane ruffles containing phospho-Src. Moreover, FLIP analysis revealed a dynamic equilibrium of Src between focal adhesions
and membrane ruffles. We conclude that upon phosphorylation, Src is directly translocated from focal adhesions to membrane
ruffles, thereby promoting formation of new adhesion complexes.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Received 21 July 2008; received after revision 10 October 2008; accepted 03 November 2008 相似文献
10.
p63 in epithelial development 总被引:2,自引:0,他引:2
Candi E Cipollone R Rivetti di Val Cervo P Gonfloni S Melino G Knight R 《Cellular and molecular life sciences : CMLS》2008,65(20):3126-3133
11.
Symmetric DNA sequence motifs allow the formation of palindromic protein/DNA complexes. Although symmetric protein sequence
motifs are less common, recent structural discoveries have unraveled a few protein/protein complexes with palindromic symmetry.
Remarkably, symmetric protein/protein complexes can be generated either by adjacent or remote sequence motifs, which may be
repeated or inverted. This contribution reflects and comments on recent findings of palindromic protein/protein complexes.
Received 14 May 2008; received after revision 21 June 2008; accepted 14 July 2008 相似文献
12.
Diverse molecular functions of Hu proteins 总被引:1,自引:1,他引:0
13.
Cowan-Jacob SW 《Cellular and molecular life sciences : CMLS》2006,63(22):2608-2625
Our current understanding of the structure, mechanism of action and modes of regulation of the protein tyrosine kinase family
owes a great deal to structural biology. Structures are now available for more than 20 different tyrosine kinase domains,
many of these in multiple conformational states. They form the basis for the design of experiments to further investigate
the role of different structural elements in the normal function and regulation of the protein and in the pathogenesis of
many human diseases. Once thought to be too similar to be specifically inhibited by a small molecule, structural differences
between kinases allow the design of compounds which inhibit only an acceptable few. This review gives a general overview of
protein tyrosine kinase structural biology, including a discussion of the strengths and limitations of the investigative methods
involved.
Received 2 May 2006; received after revision 21 June 2006; accepted 9 August 2006 相似文献
14.
Welcome the Family of FANCJ-like Helicases to the Block of Genome Stability Maintenance Proteins 总被引:1,自引:0,他引:1
Y. Wu A. N. Suhasini R. M. Brosh Jr. 《Cellular and molecular life sciences : CMLS》2009,66(7):1209-1222
The FANCJ family of DNA helicases is emerging as an important group of proteins for the prevention of human disease, cancer,
and chromosomal instability. FANCJ was identified by its association with breast cancer, and is implicated in Fanconi Anemia.
Proteins with sequence similarity to FANCJ are important for maintenance of genomic stability. Mutations in genes encoding
proteins related to FANCJ, designated ChlR1 in human and Chl1p in yeast, result in sister chromatid cohesion defects. Nematodes
mutated in dog-1 show germline as well as somatic deletions in genes containing guanine-rich DNA. Rtel knockout mice are embryonic lethal, and embryonic stem cells show telomere loss and chromosomal instability. FANCJ also shares
sequence similarity with human XPD and yeast RAD3 helicases required for nucleotide excision repair. The recently solved structure
of XPD has provided new insight to the helicase core and accessory domains of sequence related Superfamily 2 helicases. The
functions and roles of members of the FANCJ-like helicase family will be discussed.
Received 17 September 2008; received after revision 24 October 2008; accepted 28 October 2008 相似文献
15.
Brooks L Heimsath EG Loring GL Brenner C 《Cellular and molecular life sciences : CMLS》2008,65(21):3458-3466
Despite the common occurrence of forkhead associated (FHA) phosphopeptide-binding domains and really interesting new gene
(RING) E3 ubiquitin ligase domains, gene products containing both an N-terminal FHA domain and C-terminal RING domain constitute
a highly distinctive intersection. Characterized FHA-RING ligases include the two vertebrate proteins, Checkpoint with FHA
and RING (Chfr) and RING finger 8 (Rnf8), as well as three fungal proteins, Defective in mitosis (Dma1), Chf1 and Chf2. These
FHA-RING ligases play roles in negative regulation of the cell division cycle, apparently by coupling protein phosphorylation
events to specific ubiquitylation of target proteins. Here, the available data on upstream and downstream regulation of and
by FHA-RING ligases are reviewed.
Received 24 April 2008; received after revision 18 June 2008; accepted 20 June 2008 相似文献
16.
AMP-activated protein kinase in skeletal muscle: From structure and localization to its role as a master regulator of cellular metabolism 总被引:1,自引:0,他引:1
Witczak CA Sharoff CG Goodyear LJ 《Cellular and molecular life sciences : CMLS》2008,65(23):3737-3755
The AMP-activated protein kinase (AMPK) is a metabolite sensing serine/threonine kinase that has been termed the master regulator
of cellular energy metabolism due to its numerous roles in the regulation of glucose, lipid, and protein metabolism. In this
review, we first summarize the current literature on a number of important aspects of AMPK in skeletal muscle. These include
the following: (1) the structural components of the three AMPK subunits (i.e. AMPKα, β, and γ), and their differential localization
in response to stimulation in muscle; (2) the biochemical regulation of AMPK by AMP, protein phosphatases, and its three known
upstream kinases, LKB1, Ca2+/calmodulin-dependent protein kinase kinase (CaMKK), and transforming growth factor-β-activated kinase 1 (TAK1); (3) the pharmacological
agents that are currently available for the activation and inhibition of AMPK; (4) the physiological stimuli that activate
AMPK in muscle; and (5) the metabolic processes that AMPK regulates in skeletal muscle.
Received 04 May 2008; received after revision 14 June 2008; accepted 14 July 2008 相似文献
17.
The Vps10p-domain receptor family 总被引:1,自引:1,他引:0
Guido Hermey 《Cellular and molecular life sciences : CMLS》2009,66(16):2677-2689
The family of mammalian type-I transmembrane receptors containing a Vps10p domain contains five members, Sortilin, SorCS1,
SorCS2, SorCS3, and SorLA. The common characteristic of these receptors is an N-terminal Vps10p domain, which either represents
the only module of the luminal/extracellular moiety or is combined with additional domains. Family members play roles in protein
transport and signal transduction. The individual receptors bind and internalize a variety of ligands, such as neuropeptides
and trophic factors, and Sortilin and SorLA mediate trans-Golgi network-to-endosome sorting. Their prominent neuronal expression, several of the identified ligands, and recent results
support the notion that members of this receptor family have important functions in neurogenesis, plasticity-related processes,
and functional maintenance of the nervous system. For instance, it has been demonstrated that Sortilin partakes in the transduction
of proapoptotic effects, and there is converging biochemical and genetic evidence that implies that SorLA is an Alzheimer’s
disease risk factor. 相似文献
18.
The multifunctional roles of the four-and-a-half-LIM only protein FHL2 总被引:15,自引:1,他引:14
Johannessen M Møller S Hansen T Moens U Van Ghelue M 《Cellular and molecular life sciences : CMLS》2006,63(3):268-284
19.
Jegan Iyyathurai Nan Wang Catheleyne D’hondt Jean X. Jiang Luc Leybaert Geert Bultynck 《Cellular and molecular life sciences : CMLS》2018,75(11):2059-2073
Connexin 43 (Cx43) hemichannels establish local signaling networks via the release of ATP and other molecules, but their excessive opening may result in cell death. Hence, the activity of Cx43-hemichannels ought to be critically controlled. This involves interactions between the C-terminal tail (CT) and the cytoplasmic loop (CL), more particularly the L2 domain within CL. Previous work revealed an important role for the last nine amino acids of the Cx43 CT by targeting the L2 domain, as these nine amino acids were sufficient to restore the activity of CT-truncated Cx43-hemichannels. However, we discovered that deletion of the last 19 amino acids of the CT only partially lowered the binding to the L2 domain, indicating that a second L2-binding region is present in the CT. We here provide evidence that the SH3-binding domain is another CT region that targets the L2 domain. At the functional level, the SH3-binding domain was able to restore the activity of CT-truncated Cx43-hemichannels and alleviate the inhibition of full-length Cx43-hemichannels by high intracellular Ca2+ concentration ([Ca2+]i) as demonstrated by various approaches including patch clamp studies of unitary Cx43-hemichannel activity. Finally, we show that in full-length Cx43-hemichannels, deletion of either the SH3-binding domain or the CT9 region suppresses the hemichannel activity, while deletion of both domains completely annihilates the hemichannel activity. These results demonstrate that the Cx43 SH3-binding domain, in addition to the CT9 region, critically controls hemichannel activity at high [Ca2+]i, which may be involved in pathological hemichannel opening. 相似文献
20.
Novel regulation and function of Src tyrosine kinase 总被引:4,自引:0,他引:4
Src tyrosine kinase is a critical signal transducer that modulates a wide variety of cellular functions. Misregulation of
Src leads to cell transformation and cancer. Heterotrimeric guanine-nucleotide-binding proteins (G proteins) are another group
of signaling molecules that transduce signals from cell-surface receptors to generate physiological responses. Recently, it
was discovered that Gαs and Gαi could directly stimulate Src family tyrosine kinase activity. This novel regulation of Src
tyrosine kinase by G proteins provides insights into the adenylyl cyclase-independent signaling mechanisms involved in ligand-induced
receptor desensitization, internalization and other physiological processes.
Received 17 August 2001; received after revision 22 October 2001; accepted 24 October 2001 相似文献