Scientific Commons: S. E. Shoelson

Evidence for a role for the phosphotyrosine-binding domain of Shc in interleukin 2 signaling.

Ravichandran, K S, Igras, V, Shoelson, S E, Fesik, S W, Burakoff, S J

Stimulation via the T-cell growth factor interleukin 2 (IL-2) leads to tyrosine phosphorylation of Shc, the interaction of Shc with Grb2, and the Ras GTP/GDP exchange factor, mSOS. Shc also...

T-cell antigen CD28 interacts with the lipid kinase phosphatidylinositol 3-kinase by a cytoplasmic Tyr(P)-Met-Xaa-Met motif.

Prasad, K V, Cai, Y C, Raab, M, Duckworth, B, Cantley, L, Shoelson, S E, ...

The T-cell antigen CD28 provides a costimulatory signal that is required for T-cell proliferation. T-cell receptor zeta/CD3 engagement without CD28 ligation leads to a state of...

Rapid T-cell receptor-mediated tyrosine phosphorylation of p120, an Fyn/Lck Src homology 3 domain-binding protein.

Reedquist, K A, Fukazawa, T, Druker, B, Panchamoorthy, G, Shoelson, S E, Band, H

Tyrosine phosphorylation of cellular proteins is the earliest identifiable event following T-cell antigen receptor (TCR) stimulation and is essential for activating downstream signaling machinery....

Paradoxical structure and function in a mutant human insulin associated with diabetes mellitus.

Hua, Q X, Shoelson, S E, Inouye, K, Weiss, M A

The solution structure of a diabetes-associated mutant human insulin (insulin Los Angeles; PheB24-->Ser) was determined by 13C-edited NMR spectroscopy and distance-geometry/simulated annealing...

Kinetics of p56lck and p60src Src homology 2 domain binding to tyrosine-phosphorylated peptides determined by a competition assay or surface plasmon resonance.

Payne, G, Shoelson, S E, Gish, G D, Pawson, T, Walsh, C T

Src homology 2 (SH2) domains are phosphotyrosine-binding modules found within various signal-transducing proteins. We have determined by 125I competition assay and surface plasmon resonance that the...

Optimizing transmembrane domain helicity accelerates insulin receptor internalization and lateral mobility.

Goncalves, E, Yamada, K, Thatte, H S, Backer, J M, Golan, D E, Kahn, C R, ...

Transmembrane (TM) domains of integral membrane proteins are generally thought to be helical. However, a Gly-Pro sequence within the TM domain of the insulin receptor is predicted to act as a helix...

Substitution of the erbB-2 oncoprotein transmembrane domain activates the insulin receptor and modulates the action of insulin and insulin-receptor substrate 1.

Cheatham, B, Shoelson, S E, Yamada, K, Goncalves, E, Kahn, C R

The mechanism through which insulin binding to the extracellular domain of the insulin receptor activates the intrinsic tyrosine kinase in the intracellular domain of the protein is unknown. For the...

YMXM motifs of IRS-1 define substrate specificity of the insulin receptor kinase.

Shoelson, S E, Chatterjee, S, Chaudhuri, M, White, M F

Of 34 tyrosine residues in insulin receptor substrate 1 (IRS-1), 14 are adjacent to acidic residues, suggesting that they might be phosphorylation sites. Synthetic peptides corresponding to sequences...

Cellular effects of phosphotyrosine-binding domain inhibitors on insulin receptor signaling and trafficking.

Giorgetti-Peraldi, S, Ottinger, E, Wolf, G, Ye, B, Burke, T R, Shoelson, S E

Shc and insulin receptor substrate 1 (IRS-1) are cytoplasmic substrates of tyrosine kinase receptors that engage, localize, and activate downstream SH2 enzymes. Each contains a...

Interaction of Shc with Grb2 regulates association of Grb2 with mSOS.

Ravichandran, K S, Lorenz, U, Shoelson, S E, Burakoff, S J

The adapter protein Shc has been implicated in Ras signaling via many receptors, including the T-cell antigen receptor (TCR), B-cell antigen receptor, interleukin-2 receptor, interleukin-3 receptor,...

Specific motifs recognized by the SH2 domains of Csk, 3BP2, fps/fes, GRB-2, HCP, SHC, Syk, and Vav.

Songyang, Z, Shoelson, S E, McGlade, J, Olivier, P, Pawson, T, Bustelo, X R, ...

Src homology 2 (SH2) domains provide specificity to intracellular signaling by binding to specific phosphotyrosine (phospho-Tyr)-containing sequences. We recently developed a technique using a...

Identification and characterization of a high-affinity interaction between v-Crk and tyrosine-phosphorylated paxillin in CT10-transformed fibroblasts.

Birge, R B, Fajardo, J E, Reichman, C, Shoelson, S E, Songyang, Z, Cantley, L C, ...

The genome of avian sarcoma virus CT10 encodes a fusion protein in which viral Gag sequences are fused to cellular Crk sequences containing primarily Src homology 2 (SH2) and Src homology 3 (SH3)...

Insulin-stimulated oocyte maturation requires insulin receptor substrate 1 and interaction with the SH2 domains of phosphatidylinositol 3-kinase.

Chuang, L M, Myers, M G, Backer, J M, Shoelson, S E, White, M F, Birnbaum, M J, ...

Xenopus oocytes from unprimed frogs possess insulin-like growth factor I (IGF-I) receptors but lack insulin and IGF-I receptor substrate 1 (IRS-1), the endogenous substrate of this kinase, and fail...

Specific phosphopeptide binding regulates a conformational change in the PI 3-kinase SH2 domain associated with enzyme activation.

Shoelson, S E, Sivaraja, M, Williams, K P, Hu, P, Schlessinger, J, Weiss, M A

SH2 (src-homology 2) domains define a newly recognized binding motif that mediates the physical association of target phosphotyrosyl proteins with downstream effector enzymes. An example of such...

Biochemical and clinical implications of proinsulin conversion intermediates.

Given, B D, Cohen, R M, Shoelson, S E, Frank, B H, Rubenstein, A H, Tager, H S

Since a complete map of insulin-related peptides in humans requires consideration of proinsulin, Arg32/Glu33-split proinsulin, Arg65/Gly66-split proinsulin, des-Arg31,Arg32-proinsulin, des-Lys64,...

Familial hyperproinsulinemia. Two cohorts secreting indistinguishable type II intermediates of proinsulin conversion.

Robbins, D C, Shoelson, S E, Rubenstein, A H, Tager, H S

Familial hyperproinsulinemia, a hereditary syndrome in which individuals secrete high amounts of 9,000-mol wt proinsulin-like material, has been identified in two unrelated cohorts. Separate analysis...

Human insulin B24 (Phe----Ser). Secretion and metabolic clearance of the abnormal insulin in man and in a dog model.

Shoelson, S E, Polonsky, K S, Zeidler, A, Rubenstein, A H, Tager, H S

We have already demonstrated that a hyperinsulinemic, diabetic subject secreted an abnormal insulin in which serine replaced phenylalanine B24 (Shoelson S., M. Fickova, M. Haneda, A. Nahum, G. Musso,...

Plasma somatostatin 28 increases in response to feeding in man.

Polonsky, K S, Shoelson, S E, Docherty, H M

Tissue somatostatin-like immunoreactivity (SLI) consists of a number of molecular species including the cyclic tetradecapeptide or SRIF, an N-terminally extended form of SRIF termed somatostatin-28,...

Phosphatidylinositol 3'-kinase is activated by association with IRS-1 during insulin stimulation.

Backer, J M, Myers, M G, Shoelson, S E, Chin, D J, Sun, X J, Miralpeix, M, ...

IRS-1 undergoes rapid tyrosine phosphorylation during insulin stimulation and forms a stable complex containing the 85 kDa subunit (p85) of the phosphatidylinositol (PtdIns) 3'-kinase, but p85 is not...

Dileucine-based sorting signals bind to the beta chain of AP-1 at a site distinct and regulated differently from the tyrosine-based motif-binding site.

Rapoport, I, Chen, Y C, Cupers, P, Shoelson, S E, Kirchhausen, T

In previous work, we showed that peptides from endocytosed proteins containing the tyrosine YXXphi sorting motif are recognized by the mu 2 subunit of AP-2, the plasma membrane clathrin adaptor...

SH2 domains exhibit high-affinity binding to tyrosine-phosphorylated peptides yet also exhibit rapid dissociation and exchange.

Felder, S, Zhou, M, Hu, P, Ureña, J, Ullrich, A, Chaudhuri, M, ...

src homology 2 (SH2) domains of intracellular signaling molecules such as phospholipase C-gamma and phosphatidylinositol 3'-kinase-associated protein p85 represent recognition motifs for specific...