Mechanisms of CAS substrate domain tyrosine phosphorylation by FAK and Src.

Abstract:

:Tyrosine phosphorylation of CAS (Crk-associated substrate, p130(Cas)) has been implicated as a key signaling step in integrin control of normal cellular behaviors, including motility, proliferation, and survival. Aberrant CAS tyrosine phosphorylation may contribute to cell transformation by certain oncoproteins, including v-Crk and v-Src, and to tumor growth and metastasis. The CAS substrate domain (SD) contains 15 Tyr-X-X-Pro motifs, which are thought to represent the major tyrosine phosphorylation sites and to function by recruiting downstream signaling effectors, including c-Crk and Nck. CAS makes multiple interactions, direct and indirect, with the tyrosine kinases Src and focal adhesion kinase (FAK), and as a result of this complexity, several plausible models have been proposed for the mechanism of CAS-SD phosphorylation. The objective of this study was to provide experimental tests of these models in order to determine the most likely mechanism(s) of CAS-SD tyrosine phosphorylation by FAK and Src. In vitro kinase assays indicated that FAK has a very poor capacity to phosphorylate CAS-SD, relative to Src. However, FAK expression along with Src was found to be important for achieving high levels of CAS tyrosine phosphorylation in COS-7 cells, as well as recovery of CAS-associated Src activity toward the SD. Structure-functional studies for both FAK and CAS further indicated that FAK plays a major role in regulating CAS-SD phosphorylation by acting as a docking or scaffolding protein to recruit Src to phosphorylate CAS, while a secondary FAK-independent mechanism involves Src directly bound to the CAS Src-binding domain (SBD). Our results do not support models in which FAK either phosphorylates CAS-SD directly or phosphorylates CAS-SBD to promote Src binding to this site.

journal_name

Mol Cell Biol

authors

Ruest PJ,Shin NY,Polte TR,Zhang X,Hanks SK

doi

10.1128/MCB.21.22.7641-7652.2001

subject

Has Abstract

pub_date

2001-11-01 00:00:00

pages

7641-52

issue

22

eissn

0270-7306

issn

1098-5549

journal_volume

21

pub_type

杂志文章
  • Suppression of oxidative damage by Saccharomyces cerevisiae ATX2, which encodes a manganese-trafficking protein that localizes to Golgi-like vesicles.

    abstract::Oxygen toxicity in Saccharomyces cerevisiae lacking the copper/zinc superoxide dismutase (SOD1) can be suppressed by overexpression of the S. cerevisiae ATX2 gene. Multiple copies of ATX2 were found to reverse the aerobic auxotrophies of sod1(delta) mutants for lysine and methionine and also to enhance the resistance ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.16.11.6303

    authors: Lin SJ,Culotta VC

    更新日期:1996-11-01 00:00:00

  • Discrete human dihydrofolate reductase gene transcripts present in polysomal RNA map with their 5' ends several hundred nucleotides upstream of the main mRNA start site.

    abstract::The 5' ends of dihydrofolate reductase (DHFR)-specific transcripts have been mapped in the 5'-flanking region of the amplified DHFR gene of the human methotrexate-resistant cell line 6A3 by primer extension and S1 protection experiments. The main 5' end, at position -71 relative to the first nucleotide of the DHFR rea...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.5.3.493

    authors: Masters JN,Attardi G

    更新日期:1985-03-01 00:00:00

  • Raf kinase inhibitory protein function is regulated via a flexible pocket and novel phosphorylation-dependent mechanism.

    abstract::Raf kinase inhibitory protein (RKIP/PEBP1), a member of the phosphatidylethanolamine binding protein family that possesses a conserved ligand-binding pocket, negatively regulates the mammalian mitogen-activated protein kinase (MAPK) signaling cascade. Mutation of a conserved site (P74L) within the pocket leads to a lo...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01271-08

    authors: Granovsky AE,Clark MC,McElheny D,Heil G,Hong J,Liu X,Kim Y,Joachimiak G,Joachimiak A,Koide S,Rosner MR

    更新日期:2009-03-01 00:00:00

  • Death receptor-induced activation of the Chk2- and histone H2AX-associated DNA damage response pathways.

    abstract::TRAIL is an endogenous death receptor ligand also used therapeutically because of its selective proapoptotic activity in cancer cells. In the present study, we examined chromatin alterations induced by TRAIL and show that TRAIL induces a rapid activation of DNA damage response (DDR) pathways with histone H2AX, Chk2, A...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00581-08

    authors: Solier S,Sordet O,Kohn KW,Pommier Y

    更新日期:2009-01-01 00:00:00

  • Genetic dissection of the vav2-rac1 signaling axis in vascular smooth muscle cells.

    abstract::Vascular smooth muscle cells (vSMCs) are key in the regulation of blood pressure and the engagement of vascular pathologies, such as hypertension, arterial remodeling, and neointima formation. The role of the Rac1 GTPase in these cells remains poorly characterized. To clarify this issue, we have utilized genetically e...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01066-14

    authors: Fabbiano S,Menacho-Márquez M,Sevilla MA,Albarrán-Juárez J,Zheng Y,Offermanns S,Montero MJ,Bustelo XR

    更新日期:2014-12-01 00:00:00

  • Detection of two chromatin proteins which bind specifically to the 5'-flanking region of the rat prolactin gene.

    abstract::We employed a protein gel blotting procedure to search for nuclear proteins from rat pituitary cells that bind preferentially to the 5'-flanking region of the rat prolactin gene. By gel blots of chromatin proteins from GH3 rat pituitary tumor cells with a 32P-labeled prolactin genomic clone, we detected two major bind...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.5.11.2967

    authors: White BA,Preston GM,Lufkin TC,Bancroft C

    更新日期:1985-11-01 00:00:00

  • Differential effects of Cdc68 on cell cycle-regulated promoters in Saccharomyces cerevisiae.

    abstract::Swi4 and Swi6 form a complex which is required for Start-dependent activation of HO and for high-level expression of G1 cyclin genes CLN1 and CLN2. To identify other regulators of this pathway, we screened for dominant, recessive, conditional, and allele-specific suppressors of swi4 mutants. We isolated 16 recessive s...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.14.11.7455

    authors: Lycan D,Mikesell G,Bunger M,Breeden L

    更新日期:1994-11-01 00:00:00

  • Deletions of N-terminal sequences of polyoma virus T-antigens reduce but do not abolish transformation of rat fibroblasts.

    abstract::Polyoma virus transforms, upon infection or DNA transfection, nonpermissive Fisher rat fibroblasts. Cloned viral DNA was deleted of sequences around the Bg/I site at nucleotide 86 by Bal31 nuclease treatment and then recloned in Escherichia coli. The extent of deletion for each mutant was then determined by DNA sequen...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.2.10.1238

    authors: Katinka M,Yaniv M

    更新日期:1982-10-01 00:00:00

  • Wnt proteins induce dishevelled phosphorylation via an LRP5/6- independent mechanism, irrespective of their ability to stabilize beta-catenin.

    abstract::Wnt glycoproteins play essential roles in the development of metazoan organisms. Many Wnt proteins, such as Wnt1, activate the well-conserved canonical Wnt signaling pathway, which results in accumulation of beta-catenin in the cytosol and nucleus. Other Wnts, such as Wnt5a, activate signaling mechanisms which do not ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.24.11.4757-4768.2004

    authors: González-Sancho JM,Brennan KR,Castelo-Soccio LA,Brown AM

    更新日期:2004-06-01 00:00:00

  • Alternate utilization of two regulatory domains within the Moloney murine sarcoma virus long terminal repeat.

    abstract::The Moloney murine sarcoma virus long terminal repeat (LTR) harbors two distinct positive activators of transcription, namely, a distal signal and an enhancer. In this report we demonstrate that infection by herpes simplex virus (HSV) can markedly affect the utilization of these two Moloney murine sarcoma virus transc...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.5.8.1959

    authors: Graves BJ,Eisenberg SP,Coen DM,McKnight SL

    更新日期:1985-08-01 00:00:00

  • Targeting SQSTM1/p62 induces cargo loading failure and converts autophagy to apoptosis via NBK/Bik.

    abstract::In selective autophagy, the adaptor protein SQSTM1/p62 plays a critical role in recognizing/loading cargo (e.g., malfolded proteins) into autophagosomes for lysosomal degradation. Here we report that whereas SQSTM1/p62 levels fluctuated in a time-dependent manner during autophagy, inhibition or knockdown of Cdk9/cycli...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01383-13

    authors: Chen S,Zhou L,Zhang Y,Leng Y,Pei XY,Lin H,Jones R,Orlowski RZ,Dai Y,Grant S

    更新日期:2014-09-15 00:00:00

  • Nonsense codons can reduce the abundance of nuclear mRNA without affecting the abundance of pre-mRNA or the half-life of cytoplasmic mRNA.

    abstract::The abundance of the mRNA for human triosephosphate isomerase (TPI) is decreased to approximately 20% of normal by frameshift and nonsense mutations that cause translation to terminate at a nonsense codon within the first three-fourths of the reading frame. Results of previous studies inhibiting RNA synthesis with act...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.3.1892

    authors: Cheng J,Maquat LE

    更新日期:1993-03-01 00:00:00

  • B-myc inhibits neoplastic transformation and transcriptional activation by c-myc.

    abstract::B-myc is a recently described myc gene whose product has not been functionally characterized. The predicted product of B-myc is a 168-amino-acid protein with extensive homology to the c-Myc amino-terminal region, previously shown to contain a transcriptional activation domain. We hypothesized that B-Myc might also fun...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.2.1130

    authors: Resar LM,Dolde C,Barrett JF,Dang CV

    更新日期:1993-02-01 00:00:00

  • The T-cell oncogenic protein HOX11 activates Aldh1 expression in NIH 3T3 cells but represses its expression in mouse spleen development.

    abstract::Hox11 is a homeobox gene essential for spleen formation in mice, since atrophy of the anlage of a developing spleen occurs in early embryonic development in Hox11 null mice. HOX11 is also expressed in a subset of T-cell acute leukemias after specific chromosomal translocations. Since the protein has a homeodomain and ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.18.12.7030

    authors: Greene WK,Bahn S,Masson N,Rabbitts TH

    更新日期:1998-12-01 00:00:00

  • Selective degradation of early-response-gene mRNAs: functional analyses of sequence features of the AU-rich elements.

    abstract::The metabolic lifetime of mRNA can be specified by specific cis-acting elements within mRNA. One type of element is an adenylate- and uridylate-rich element (ARE) found in the 3' untranslated region of many highly unstable mRNAs for mammalian early-response genes (ERGs). Among the better-characterized members of the E...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.14.12.8471

    authors: Chen CY,Shyu AB

    更新日期:1994-12-01 00:00:00

  • Hepatocyte nuclear factor 3/fork head homolog 11 is expressed in proliferating epithelial and mesenchymal cells of embryonic and adult tissues.

    abstract::The hepatocyte nuclear factor 3alpha (HNF-3alpha) and 3beta proteins have homology in the winged helix/fork head DNA binding domain and regulate cell-specific transcription in hepatocytes and in respiratory and intestinal epithelia. In this study, we describe two novel isoforms of the winged helix transcription factor...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.3.1626

    authors: Ye H,Kelly TF,Samadani U,Lim L,Rubio S,Overdier DG,Roebuck KA,Costa RH

    更新日期:1997-03-01 00:00:00

  • Bcl-3 expression promotes cell survival following interleukin-4 deprivation and is controlled by AP1 and AP1-like transcription factors.

    abstract::We have analyzed the interleukin-4 (IL-4)-triggered mechanisms implicated in cell survival and show here that IL-4 deprivation induces apoptotic cell death but does not modulate Bcl-2 or Bcl-x expression. Since Bcl-x expression is insufficient to ensure cell survival in the absence of IL-4, we speculate that additiona...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.10.3407-3416.2000

    authors: Rebollo A,Dumoutier L,Renauld JC,Zaballos A,Ayllón V,Martínez-A C

    更新日期:2000-05-01 00:00:00

  • Cooperation of p27(Kip1) and p18(INK4c) in progestin-mediated cell cycle arrest in T-47D breast cancer cells.

    abstract::The steroid hormone progesterone regulates proliferation and differentiation in the mammary gland and uterus by cell cycle phase-specific actions. The long-term effect of progestins on T-47D breast cancer cells is inhibition of cellular proliferation. This is accompanied by decreased G(1) cyclin-dependent kinase (CDK)...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.7.2581-2591.2000

    authors: Swarbrick A,Lee CS,Sutherland RL,Musgrove EA

    更新日期:2000-04-01 00:00:00

  • Genomic instability and enhanced radiosensitivity in Hsp70.1- and Hsp70.3-deficient mice.

    abstract::Heat shock proteins (HSPs) are highly conserved among all organisms from prokaryotes to eukaryotes. In mice, the HSP genes Hsp70.1 and Hsp70.3 are induced by both endogenous and exogenous stressors, such as heat and toxicants. In order to determine whether such proteins specifically influence genomic instability, mice...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.24.2.899-911.2004

    authors: Hunt CR,Dix DJ,Sharma GG,Pandita RK,Gupta A,Funk M,Pandita TK

    更新日期:2004-01-01 00:00:00

  • Bone-specific transcription factor Runx2 interacts with the 1alpha,25-dihydroxyvitamin D3 receptor to up-regulate rat osteocalcin gene expression in osteoblastic cells.

    abstract::Bone-specific transcription of the osteocalcin (OC) gene is regulated principally by the Runx2 transcription factor and is further stimulated in response to 1alpha,25-dihydroxyvitamin D3 via its specific receptor (VDR). The rat OC gene promoter contains three recognition sites for Runx2 (sites A, B, and C). Mutation o...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.24.20.8847-8861.2004

    authors: Paredes R,Arriagada G,Cruzat F,Villagra A,Olate J,Zaidi K,van Wijnen A,Lian JB,Stein GS,Stein JL,Montecino M

    更新日期:2004-10-01 00:00:00

  • RIP1 Cleavage in the Kinase Domain Regulates TRAIL-Induced NF-κB Activation and Lymphoma Survival.

    abstract::Although TRAIL is considered a potential anticancer agent, it enhances tumor progression by activating NF-κB in apoptosis-resistant cells. Cellular FLICE-like inhibitory protein (cFLIP) overexpression and caspase-8 activation have been implicated in TRAIL-induced NF-κB activation; however, the underlying mechanisms ar...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00692-15

    authors: Zhang L,Blackwell K,Workman LM,Chen S,Pope MR,Janz S,Habelhah H

    更新日期:2015-10-01 00:00:00

  • Functional cooperation between the proteins Nck and ADAP is fundamental for actin reorganization.

    abstract::T cell antigen receptor (TCR) activation triggers profound changes in the actin cytoskeleton. In addition to controlling cellular shape and polarity, this process regulates vital T cell responses, such as T cell adhesion, motility, and proliferation. These depend on the recruitment of the signaling proteins Nck and Wi...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01358-10

    authors: Pauker MH,Reicher B,Fried S,Perl O,Barda-Saad M

    更新日期:2011-07-01 00:00:00

  • Identification of the crossover site during FLP-mediated recombination in the Saccharomyces cerevisiae plasmid 2 microns circle.

    abstract::The FLP protein of the Saccharomyces cerevisiae plasmid 2 microns circle catalyzes site-specific recombination between two repeated segments present on the plasmid. In this paper we present results of experiments we performed to define more precisely the features of the FLP recognition target site, which we propose to...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.6.10.3357

    authors: McLeod M,Craft S,Broach JR

    更新日期:1986-10-01 00:00:00

  • Negative regulation contributes to tissue specificity of the immunoglobulin heavy-chain enhancer.

    abstract::We have identified in and around the immunoglobulin heavy-chain enhancer two apparently distinct negative regulatory elements which repress immunoglobulin H enhancer, simian virus 40 enhancer, and heterologous promoter activity in fibroblasts but not in myeloma cells. We propose that in nonlymphoid cells, negative reg...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.7.7.2558

    authors: Imler JL,Lemaire C,Wasylyk C,Wasylyk B

    更新日期:1987-07-01 00:00:00

  • Growth Differentiation Factor 15 Maturation Requires Proteolytic Cleavage by PCSK3, -5, and -6.

    abstract::Growth differentiation factor 15 (GDF15) is a secreted protein with pleotropic functions from the transforming growth factor β (TGF-β) family. GDF15 is synthesized as a precursor and undergoes proteolytic cleavage to generate mature GDF15. The strong appetite-suppressing effect of mature GDF15 makes it an attractive t...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00249-18

    authors: Li JJ,Liu J,Lupino K,Liu X,Zhang L,Pei L

    更新日期:2018-10-15 00:00:00

  • Requirement for a functional interaction between mediator components Med6 and Srb4 in RNA polymerase II transcription.

    abstract::Regulated transcription of class II genes of the yeast Saccharomyces cerevisiae requires the diverse functions of mediator complex. In particular, MED6 is essential for activated transcription from many class II promoters, suggesting that it functions as a key player in the relay of activator signals to the basal tran...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.18.9.5364

    authors: Lee YC,Kim YJ

    更新日期:1998-09-01 00:00:00

  • A novel in vivo transcription assay demonstrates the presence of globin-inducing trans-acting factors in uninduced murine erythroleukemia cells.

    abstract::We report the development of a novel in vivo transcription assay for trans-acting factors regulating the human gamma- and beta-globin genes. A cDNA coding for the human tissue-type plasminogen activator (t-PA) was inserted into the globin genes. Simian virus 40 small T-antigen splice and polyadenylation signals were i...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.8.1.130

    authors: Wrighton N,Grosveld F

    更新日期:1988-01-01 00:00:00

  • Intramolecular disulfide bonds of the prolactin receptor short form are required for its inhibitory action on the function of the long form of the receptor.

    abstract::The short form (S1b) of the prolactin receptor (PRLR) silences prolactin-induced activation of gene transcription by the PRLR long form (LF). The functional and structural contributions of two intramolecular disulfide (S-S) bonds within the extracellular subdomain 1 (D1) of S1b to its inhibitory function on the LF wer...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01716-08

    authors: Xie YL,Hassan SA,Qazi AM,Tsai-Morris CH,Dufau ML

    更新日期:2009-05-01 00:00:00

  • Molecular basis for telomere repeat divergence in budding yeast.

    abstract::Telomerase is a ribonucleoprotein enzyme that adds repetitive sequences to the ends of linear chromosomes, thereby counteracting nucleotide loss due to incomplete replication. A short region of the telomerase RNA subunit serves as template for nucleotide addition onto the telomere 3' end. Although Saccharomyces cerevi...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.21.21.7277-7286.2001

    authors: Förstemann K,Lingner J

    更新日期:2001-11-01 00:00:00

  • Inhibition of phorbol ester-receptor binding by a factor from human serum.

    abstract::The inhibition of receptor binding of [3H]phorbol-12,13-dibutyrate (PDBu) by a factor from human serum was characterized. The serum factor inhibited [3H]PDBu binding in intact monolayer cultures of the rat embryo cell line CREF N and in a subcellular system containing membranes from these cells. Inhibition occurred at...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.2.5.545

    authors: Horowitz AD,Greenebaum E,Nicolaides M,Woodward K,Weinstein IB

    更新日期:1982-05-01 00:00:00