The insulin receptor substrates (IRSs) function in insulin signaling. Four members of the family, IRS-1 through IRS-4, are known. Previously, mice with targeted disruption of the genes for IRS-1, -2, and -3 have been characterized. To examine the physiological role of IRS-4, we have generated and characterized mice lacking IRS-4. Male IRS-4-null mice were approximately 10% smaller in size than ...

Let G1, G2, . . . , Gt be graphs. The multicolor Ramsey number R(G1, G2, . . . , Gt) is the smallest positive integer n such that if the edges of a complete graph Kn are partitioned into t disjoint color classes giving t graphs H1,H2, . . . ,Ht, then at least one Hi has a subgraph isomorphic to Gi. In this paper, we provide the exact value of R(Pn1 , Pn2 , . . . , Pnt , Ck) for certain values o...

Hoàng defined the P4-sparse graphs as the graphs where every set of five vertices induces at most one P4. These graphs attracted considerable attention in connection with the P4-structure of graphs and the fact that P4-sparse graphs have bounded clique-width. Fouquet and Giakoumakis generalized this class to the nicely structured semi-P4-sparse graphs being the (P5, co-P5, co-chair)-free graphs...

Peptidases are classical objects of enzymology and structural studies. However, a few protein families with experimentally characterized proteolytic activity, but unknown catalytic mechanism and three-dimensional structures, still exist. Using comparative sequence analysis, we deduce spatial structure for one of such families, namely, U40, which contains just one P5 protein from bacteriophage p...

Tumor necrosis factor alpha (TNFalpha) inhibits insulin action, in part, through serine phosphorylation of IRS proteins; however, the phosphorylation sites that mediate the inhibition are unknown. TNFalpha promotes multipotential signal transduction cascades, including the activation of the Jun NH(2)-terminal kinase (JNK). Endogenous JNK associates with IRS-1 in Chinese hamster ovary cells. Ani...

IRS-1 (insulin receptor substrate-1) is a major substrate for the insulin receptor tyrosine kinase. After phosphorylation by the insulin receptor, IRS-1 binds to the specific molecules which possess SH2 (src homology 2) domain such as 85 kDa subunit of phosphatidylinositol 3 kinase and may mediate insulin signals. The regulation of IRS-1 has been analyzed in animal models of insulin resistance,...

In 1996, the IRS created and implemented its own website—irs.gov—to allow taxpayers easy access to IRS information and resources at their own convenience. Since the site’s inception, the IRS has relied on web analytics to assess the site’s usefulness and to make improvements to enhance the customers’ experiences and satisfaction. Serving customers and improving customer satisfaction within the ...

We have performed the first genome-wide analysis of the Inverted Repeat (IR) structure in the human genome, using a novel and efficient software package called Inverted Repeats Finder (IRF). After masking of known repetitive elements, IRF detected 22,624 human IRs characterized by arm size from 25 bp to >100 kb with at least 75% identity, and spacer length up to 100 kb. This analysis required 6...

Insulin signals are mediated through tyrosine phosphorylation of specific proteins such as insulin receptor substrate 1 (IRS-1) and Shc by the activated insulin receptor (IR). Phosphorylation of both proteins is nearly abolished by an alanine substitution at Tyr-960 (A960) in the beta-subunit of the receptor. However, overexpression of IRS-1 in CHO cells expressing the mutant receptor (A960 cel...

The insulin receptor substrate 2 (IRS-2) protein is one of the major insulinsignaling substrates. In the present study, we investigated the role of IRS-2 in skin epidermal keratinocytes and dermal fibroblasts. Even though skin is not a classical insulin target tissue, we have previously demonstrated that insulin, via the insulin receptor (IR), is essential for normal skin cell physiology. To id...