Scientific Commons: L. C. Cantley

Sequence specificity of C-terminal Src kinase (CSK)--a comparison with Src-related kinases c-Fgr and Lyn (1997)

Songyang, Z, Marin, O, Donella-Deana, A, Brunati, A M, Guerra, B, ...

An eicosapeptide encompassing the C-terminal tail of c-Src (Tyr527) which is conserved in most Src-related protein kinases, is phosphorylated by C-terminal Src kinase (CSK) and by the two Src-related...

Insect cell-expressed p180erbB3 possesses an impaired tyrosine kinase activity.

Guy, P M, Platko, J V, Cantley, L C, Cerione, R A, Carraway, K L

Protein kinases share a number of highly conserved or invariant amino acid residues in their catalytic domains, suggesting that these residues are necessary for kinase activity. In p180erbB3, a...

Src-homology 3 domain of protein kinase p59fyn mediates binding to phosphatidylinositol 3-kinase in T cells.

Prasad, K V, Janssen, O, Kapeller, R, Raab, M, Cantley, L C, Rudd, C E

The Src-related tyrosine kinase p59fyn(T) plays an important role in the generation of intracellular signals from the T-cell antigen receptor TCR zeta/CD3 complex. A key question concerns the nature...

Activation of phosphatidylinositol 3-kinase by insulin.

Ruderman, N B, Kapeller, R, White, M F, Cantley, L C

Insulin action appears to require the protein-tyrosine kinase domain of the beta subunit of the insulin receptor. Despite this, the identities and biochemical functions of the cellular targets of...

A structural basis for substrate specificities of protein Ser/Thr kinases: primary sequence preference of casein kinases I and II, NIMA, phosphorylase kinase, calmodulin-dependent kinase II, CDK5, and Erk1.

Songyang, Z, Lu, K P, Kwon, Y T, Tsai, L H, Filhol, O, Cochet, C, ...

We have developed a method to study the primary sequence specificities of protein kinases by using an oriented degenerate peptide library. We report here the substrate specificities of eight protein...

Transformation-defective mutants of polyomavirus middle T antigen associate with phosphatidylinositol 3-kinase (PI 3-kinase) but are unable to maintain wild-type levels of PI 3-kinase products in intact cells.

Ling, L E, Druker, B J, Cantley, L C, Roberts, T M

Middle T antigen (MT) of polyomavirus causes transformation by associating with a number of cellular proteins. The association with and activation of two such proteins, phosphatidylinositol 3-kinase...

Production of novel polyphosphoinositides in vivo is linked to cell transformation by polyomavirus middle T antigen.

Serunian, L A, Auger, K R, Roberts, T M, Cantley, L C

Phosphatidylinositol 3-kinase associates with the polyomavirus middle T antigen (PyMTAg)-pp60c-src complex in polyomavirus-transformed cells. Here we show that anti-PyMTAg immunoprecipitates from...

Evidence that the Rous sarcoma virus transforming gene product phosphorylates phosphatidylinositol and diacylglycerol.

Sugimoto, Y, Whitman, M, Cantley, L C, Erikson, R L

The ability of purified Rous sarcoma virus transforming gene product, pp60v-src, to phosphorylate phosphatidylinositol and diacylglycerol was investigated. Phosphatidylinositol was phosphorylated to...

ErbB3 is involved in activation of phosphatidylinositol 3-kinase by epidermal growth factor.

Soltoff, S P, Carraway, K L, Prigent, S A, Gullick, W G, Cantley, L C

Conflicting results concerning the ability of the epidermal growth factor (EGF) receptor to associate with and/or activate phosphatidylinositol (PtdIns) 3-kinase have been published. Despite the...

Activation of phosphatidylinositol 3-kinase in cells expressing abl oncogene variants.

Varticovski, L, Daley, G Q, Jackson, P, Baltimore, D, Cantley, L C

A phosphoinositide kinase specific for the D-3 position of the inositol ring, phosphatidylinositol (PI) 3-kinase, associates with activated receptors for platelet-derived growth factor, insulin, and...

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)...

Phosphatidylinositol (PI) 3-kinase and PI 4-kinase binding to the CD4-p56lck complex: the p56lck SH3 domain binds to PI 3-kinase but not PI 4-kinase.

Prasad, K V, Kapeller, R, Janssen, O, Repke, H, Duke-Cohan, J S, Cantley, L C, ...

CD4 serves as a receptor for major histocompatibility complex class II antigens and as a receptor for the human immunodeficiency virus type 1 (HIV-1) viral coat protein gp120. It is coupled to the...

Increasing the intracellular Na+ concentration induces differentiation in a pre-B lymphocyte cell line.

Rosoff, P M, Cantley, L C

The ability of lipopolysaccharide (LPS), a polyclonal B-cell mitogen, to induce differentiation in the pre-B cell tumor line 70Z/3 can be mimicked by drugs that increase the intracellular Na+...

Sequence requirements for the recognition of tyrosine-based endocytic signals by clathrin AP-2 complexes.

Boll, W, Ohno, H, Songyang, Z, Rapoport, I, Cantley, L C, Bonifacino, J S, ...

We recently determined that fusion proteins containing tyrosine-based endocytic signals bind to the mu 2 subunit of AP-2, the complex that drives clathrin coat formation and mediates endocytosis from...

Purification and characterization of human erythrocyte phosphatidylinositol 4-kinase. Phosphatidylinositol 4-kinase and phosphatidylinositol 3-monophosphate 4-kinase are distinct enzymes.

Graziani, A, Ling, L E, Endemann, G, Carpenter, C L, Cantley, L C

PtdIns 4-kinase has been purified 83,000-fold from human erythrocyte membranes. The major protein detected by SDS/PAGE is of molecular mass 56 kDa, and enzymic activity can be renatured from this...

Extracellular ATP increases free cytosolic calcium in rat parotid acinar cells. Differences from phospholipase C-linked receptor agonists.

McMillian, M K, Soltoff, S P, Lechleiter, J D, Cantley, L C, Talamo, B R

The effects of extracellular ATP on intracellular free calcium concentration [( Ca2+]i), phosphatidylinositol (PtdIns) turnover, amylase release and Ca2+-activated membrane currents were examined in...

A monoclonal antibody distinguishes two types of phosphatidylinositol 4-kinase.

Endemann, G C, Graziani, A, Cantley, L C

A monoclonal antibody has been developed against the type II PtdIns 4-kinase from bovine brain. This antibody, 4C5G, causes greater than 90% inhibition of the type II PtdIns 4-kinase from bovine...

Regulatory interactions in the recognition of endocytic sorting signals by AP-2 complexes.

Rapoport, I, Miyazaki, M, Boll, W, Duckworth, B, Cantley, L C, Shoelson, S, ...

Many plasma membrane proteins destined for endocytosis are concentrated into clathrin-coated pits through the recognition of a tyrosine-based motif in their cytosolic domains by an adaptor (AP-2)...

Juxtamembrane tyrosine residues couple the Eph family receptor EphB2/Nuk to specific SH2 domain proteins in neuronal cells.

Holland, S J, Gale, N W, Gish, G D, Roth, R A, Songyang, Z, Cantley, L C, ...

Eph-related receptor tyrosine kinases have been implicated in the control of axonal navigation and fasciculation. To investigate the biochemical mechanisms underlying such functions, we have...

Phosphatidylinositol-3,4,5-trisphosphate (PtdIns-3,4,5-P3)/Tec kinase-dependent calcium signaling pathway: a target for SHIP-mediated inhibitory signals.

Scharenberg, A M, El-Hillal, O, Fruman, D A, Beitz, L O, Li, Z, Lin, S, ...

Tec family non-receptor tyrosine kinases have been implicated in signal transduction events initiated by cell surface receptors from a broad range of cell types, including an essential role in B-cell...

A tightly associated serine/threonine protein kinase regulates phosphoinositide 3-kinase activity.

Carpenter, C L, Auger, K R, Duckworth, B C, Hou, W M, Schaffhausen, B, Cantley, L C

We identified a serine/threonine protein kinase that is associated with and phosphorylates phosphoinositide 3-kinase (PtdIns 3-kinase). The serine kinase phosphorylates both the 85- and 110-kDa...