Contributors: Lew Cantley
Artwork by: Gil R. Sambrano and Roger Sunahara

Insulin stimulates a variety of responses in cardiac myocytes, including glucose uptake, glycogen synthesis and glucose metabolism. In addition, insulin and insulin-like growth factor have been shown to promote survival of cardiac myocytes under ischemic conditions. Both hormones act via protein-Tyr kinase type receptors at the cell membrane that stimulate phosphorylation of the insulin receptor substrates 1 and 2 (IRS- and IRS-2). The phosphorylation of IRS proteins on tyrosine residues initiates a complex signal transduction cascade involving protein-Ser/Thr kinases and phosphoinositide 3-kinases that ultimately regulates glucose uptake and metabolism, protein synthesis and cell survival.
(borrowed from the Alliance for Cellular Signalling Web site- http://www.cellularsignaling.org/)

Contributors: Mike Berridge, Bill Catterall, Jim Stull, Shaun Coughlin, and Eric Olso
Artwork by: Gil R. Sambrano and Roger Sunahara

Contraction of cardiac cells is driven by Ca2+ that enters through channels in the membrane before being amplified by release of Ca2+ through ryanodine receptors (RYRs) on the internal storage organelles. These organelles also release smaller amounts of Ca2+ in response to receptor- mediated generation of inositol trisphosphate (IP3). In addition to controlling contraction, Ca2+ acts through calmodulin (CAM) to stimulate a variety of signaling pathways that have been implicated in the control of gene transcription and cardiac hypertrophy. Ca2+ signaling is modulated by G protein-coupled receptors operating through the cAMP/PKA (see the cAMP module) and the DAG/PKC messenger pathways.
(borrowed from the Alliance for Cellular Signalling Web site- http://www.cellularsignaling.org/)

Contributors: James Stull, Michael Berridge, Melanie Cobb, Peter Devreotes, and Roger Sunahara
Artwork by: Gil R. Sambrano and Roger Sunahara

Cyclic AMP (cAMP) has a dominant role in regulating many aspects of cardiac cell function. A number of receptors use different G protein subunits to activate various adenylyl cyclase isoforms to generate cAMP. Most of the actions of cAMP are mediated through protein kinase A (PKA) to regulate myocardial contraction via actions on contractile proteins, ion channels, and transporters. In addition, PKA leads to an increased flow of metabolic energy and activation of gene transcription. cAMP can also exert direct effects on downstream molecules such as Rap1GEF.
(borrowed from the Alliance for Cellular Signalling Web site- http://www.cellularsignaling.org/)

Contributors: Jason Cyster, Arthur Weiss
Artwork by: Gil R. Sambrano and Roger Sunahara
BR> This map identifies links in signaling pathways regulated by the cytokine, interleukin 4 (IL4). Stimulation of the two component IL4 receptor leads to rapid activation of Jak family tyrosine kinases. The active JAKs phosphorylate associated STAT molecules that then translocate to the nucleus, and the JAKs also cause activation of Ras-, HPK- and PI3K- containing pathways. SOCS molecules act as negative regulators of the STAT pathway, whereas negative regulators of the JAKs and of the ras, HPK and PI3K pathways are presently not included in this map. One cautionary note is that most of the links in this map are based on studies performed in transformed cell lines.
(borrowed from the Alliance for Cellular Signalling Web site- http://www.cellularsignaling.org/)

Contributors: Henry Bourne, Orion Weiner and Fei Wang
Artwork by: Gil R. Sambrano and Roger Sunahara

This map identifies links in signaling pathways that mediate chemotaxis of leukocytes. These pathways connect stimulation of G protein coupled chemokine receptors to regulation of the actin/myosin cytoskeleton. Many signal cascades converge on or are stimulated by PI(3,4,5)P3. This membrane lipid accumulates at the leading edge of neutrophils and appears to exert dual actions on Rho GTPases - that is, both as an upstream stimulator (probably of GEFs) and as a downstream mediator. One possibility is that this dual role is important for a positive feedback loop, centered on cell's the leading edge, that is responsible for conveying asymmetrical signals to the actin cytoskeleton, and therefore for morphologic polarity. The gradient of chemoattractant may bias the strength of this feedback loop toward the up-gradient edge of the cell. Our criteria for assigning links to specific pathways was inclusive rather than exclusive. Consequently, some connections in the map are well established, while pathways are in many cases poorly defined. For investigators of B cells, one additional caution is in order: the links in this map are based for the most part on studies in neutrophils and T lymphocytes.
(borrowed from the Alliance for Cellular Signalling Web site- http://www.cellularsignaling.org/)

Contributors: Gail Bishop
Artwork by: Gil R. Sambrano

This map includes pathways by which three Rho GTPases - Rac, Cdc42, and Rho itself - regulate assemblies of actin polymers in non-muscle cells. We have attempted to include only those pathways and molecules whose roles are well established.
(borrowed from the Alliance for Cellular Signalling Web site- http://www.cellularsignaling.org/)

Contributors: Art Weiss and Jason Cyster
Artwork by: Gil R. Sambrano and Roger Sunahara

Oligomerization of the B cell antigen receptor (BCR) leads to the activation of cytoplasmic tyrosine kinases. Src kinases such as Lyn regulate a multitude of phosphorylation events that also involves the activation of Syk and Tec (Btk) families of tyrosine kinases. These kinases coordinately phosphorylate downstream substrates that include adaptors such as BLNK and effectors such as phospholipase C. Ultimately, a cascade of signaling pathways, including the Ras and calcium pathways, contribute to the differentiation and proliferation of antigen-specific B cells.
(borrowed from the Alliance for Cellular Signalling Web site- http://www.cellularsignaling.org/)