HEF1, p130Cas , and Efs/Sin constitute a family of multidomain docking proteins that have been implicated in coordinating the regulation of cell adhesion. Each of these proteins contains an SH3 domain, conferring association with focal adhesion kinase; a domain rich in SH2-binding sites, phosphorylated by or associating with a number of oncoproteins, including Abl, Crk, Fyn, and others; and a highly conserved carboxy-terminal domain. In this report, we show that the HEF1 protein is processed in a complex manner, with transfection of a single cDNA resulting in the generation of at least four protein species, p115 HEF1 , p105 HEF1 , p65 HEF1 , and p55 HEF1 . We show that p115 HEF1 and p105 HEF1 are different phosphorylation states of the full-length HEF1. p55 HEF1 , however, encompasses only the amino-terminal end of the HEF1 coding sequence and arises via cleavage of full-length HEF1 at a caspase consensus site. We find that HEF1 proteins are abundantly expressed in epithelial cells derived from breast and lung tissue in addition to the lymphoid cells in which they have been predominantly studied to date. In MCF-7 cells, we find that expression of the endogenous HEF1 proteins is cell cycle regulated, with p105 HEF1 and p115 HEF1 being rapidly upregulated upon induction of cell growth, whereas p55 HEF1 is produced specifically at mitosis. While p105 HEF1 and p115 HEF1 are predominantly cytoplasmic and localize to focal adhesions, p55 HEF1 unexpectedly is shown to associate with the mitotic spindle. In support of a role at the spindle, two-hybrid library screening with HEF1 identifies the human homolog of the G 2 /M spindle-regulatory protein Dim1p as a specific interactor with a region of HEF1 encompassed in p55 HEF1 . In sum, these data suggest that HEF1 may directly connect morphological control-related signals with cell cycle regulation and thus play a role in pathways leading to the progression of cancer.

This is the author accepted manuscript. The final version is available from Taylor & Francis via http://dx.doi.org/10.1080/2150704X.2017.1280200Hyperspectral image (HSI) classification is a hot topic in the remote sensing community. This paper proposes a new framework of spectral-spatial feature extraction for HSI classification, in which for the first time the concept of deep learning is introduced. Specifically, the model of autoencoder is exploited in our framework to extract various kinds of features. First we verify the eligibility of autoencoder by following classical spectral information based classification and use autoencoders with different depth to classify hyperspectral image. Further in the proposed framework, we combine PCA on spectral dimension and autoencoder on the other two spatial dimensions to extract spectral-spatial information for classification. The experimental results show that this framework achieves the highest classification accuracy among all methods, and outperforms classical classifiers such as SVM and PCA-based SVMauthorsversionPeer reviewe

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The related adhesion focal tyrosine kinase (RAFTK) is tyrosine-phosphorylated following ␤1 integrin or B cell antigen receptor stimulation in human B cells. Two substrates that are tyrosine-phosphorylated following integrin ligation in B cells are p130Cas and the Cas family member human enhancer of filamentation 1 (HEF1), both of which can associate with RAFTK. In this report we observed that RAFTK was involved in the phosphorylation of these two proteins. While a catalytically active RAFTK was required for both p130 Cas Cas . These data suggest that RAFTK itself is sufficient for HEF1 phosphorylation, whereas a cooperation between RAFTK and Src kinases is required for the complete phosphorylation of p130Cas .The integrin family of adhesion receptors are involved in transducing signals into cells that result in diverse biologic events, such as the modulation of cell viability, proliferation, and differentiation (1-3). One of the intracellular signaling events initiated by integrins is the activation of a cascade of tyrosine phosphorylation (4). We have previously reported that the related adhesion focal tyrosine kinase, RAFTK, 1 (5) also known as PYK2 and CAK␤ (6, 7), is tyrosine-phosphorylated following ␤1 integrin or B cell antigen receptor-mediated (BCR) stimulation in both transformed and normal human B cells (8). This kinase is preferentially expressed in hematopoietic cells and neurons and is distinct from p125 FAK (focal adhesion kinase, FAK). Similar to FAK, RAFTK lacks a transmembrane region, does not contain any SH2 or SH3 domains, but does have a proline-rich region in its C terminus (9).RAFTK interacts with several proteins involved in integrin signaling including paxillin and Src kinases (9 -11). RAFTK, like FAK, also interacts constitutively with p130Cas and the Cas-like molecule human enhancer of filamentation 1 (HEF1), two proteins which are tyrosine-phosphorylated after integrin stimulation in lymphoid cells (8,(12)(13)(14). p130Cas belongs to a new family of structurally related proteins which are thought to act as "docking molecules," which also includes HEF1/Cas-L and Efs/Sin (15, 16). p130Cas is an SH3 domain-containing molecule with 15 potential Crk-SH2-binding motifs (substrate domain, SD domain), an SH3 binding motif located near the N-terminal region as well as a proline-rich sequence (RPLP-SPP) and a YDYV motif, which have been shown to bind to Src SH3 and SH2 domains, respectively, in its C-terminal region (17). HEF1 is 64% homologous to p130Cas and contains also an SH3 domain and multiple SH2 binding motifs, but lacks the proline-rich sequences located near the N-terminal SH3 domain and in the C-terminal region of p130 Cas (13). Binding of Crk family members to tyrosine phosphorylated Cas and HEF1 illustrates the assembly of signaling complexes, since the SH3 domain of Crk proteins can bind in turn to a number of proteins including two guanine nucleotide exchange factors, Sos and C3G, which regulate Ras and Rap1 activation, respectively (18 -21). The Cas and HEF1 signaling complexes...

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Irisin, a newly discovered myokine, is considered as a promising candidate for the treatment of metabolic disturbances and cardiovascular diseases. In the present study, we used two animal models, apolipoprotein E-deficient mice fed on a high-cholesterol diet and a mouse carotid partial ligation model to test the anti-atherosclerotic effect of irisin. Irisin treatment (0.5 μg/g body weight/day) significantly reduced the severity of aortic atherosclerosis in apolipoprotein E-deficient mice fed on a high-cholesterol diet and suppressed carotid neointima formation in a carotid partial ligation model. It was associated with decreased inflammation and cell apoptosis in aortic tissues. In addition, in a cell culture model, irisin restored ox-LDL-induced human umbilical vein endothelial cell dysfunction by reducing the levels of inflammatory genes via inhibiting the reactive oxygen species (ROS)/ p38 MAPK/ NF-κB signaling pathway activation and inhibiting cell apoptosis via up-regulating Bcl-2 and down-regulating Bax and caspase-3 expression. Our study demonstrated that irisin significantly reduced atherosclerosis in apolipoprotein E-deficient mice via suppressing ox-LDL-induced cell inflammation and apoptosis, which might have a direct therapeutic effect on atherosclerotic diseases.