ncbi.nlm.nih/entrez/query Books Molecular Cell Biology Lodish

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description Books Molecular Cell Biology Lodish 20. Cell-to-Cell Signaling: Hormones and Receptors. CYTOKINES: Soluble factors required for hematopoietic Cell growth and differentiation. gp130 IL-6 !L-11 LIF CNTF. gp 140 IL-3 - PowerPoint PPT Presentation

Transcript of ncbi.nlm.nih/entrez/query Books Molecular Cell Biology Lodish

  • Cell Biology Lodish20. Cell-to-Cell Signaling: Hormones and Receptors

  • CYTOKINES: Soluble factors required for hematopoietic Cell growth and differentiationIFN familyIFN/IFNIL-10gp130IL-6!L-11LIFCNTFgp 140IL-3IL-5GM-CSFc chainIL-2IL-4IL-7IL-9IL-15

  • Figure 20-5. Common intracellular signaling proteins. (a) GTP-binding proteins with GTPase activity function as molecular switches. When bound to GTP they are active; when bound to GDP, they are inactive. They fall into two categories, trimeric G proteins and Ras-like proteins(b) Protein kinases modulate the activity or the binding properties of substrate proteins by phosphorylating serine, threonine, or tyrosine residues. The phosphorylated form of some proteins is active, whereas the dephosphorylated form of other proteins is active. The combined action of kinases and phosphatases, which dephosphorylate specific substrates, can cycle proteins between active and inactive states. (c) Adapter proteins contain various protein-binding motifs that promote the formation of multiprotein signaling complexes.

  • Figure 20-6. Schematic overview of common signaling pathways downstream from G protein coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs). SM=Second messenger

  • Figure 20-9. Identification and isolation of a cDNA encoding a desired cell-surface receptor by plasmid expression cloning. All mRNA is extracted from cells that normally express the receptor and reverse-transcribed into double-stranded cDNA which is then introduced in non-expr. cells eg COSFluorescence-activated cell sorter (FACS).

  • Figure 15-47. Six subfamilies of receptor tyrosine kinases. Only one or two members of each subfamily are indicated. Note that the tyrosine kinase domain is interrupted by a "kinase insert region" in some of the subfamilies. The functional significance of the cysteine-rich and immunoglobulinlike domains is unknown.

  • Figure 20-21. General structure and activation of receptor tyrosine kinases (RTKs). The ligands for some RTKs, such as the receptor for EGF depicted here, are monomeric; ligand binding induces a conformational change in receptor monomers that promotes their dimerization. The ligands for other RTKs are dimeric; their binding brings two receptor monomers together directly (see Figure 20-4d). In either case, the kinase activity of each subunit of the dimeric receptor initially phosphorylates tyrosine residues near the catalytic site in the other subunit. Subsequently, tyrosine residues in other parts of the cytosolic domain are autophosphorylated. See text for discussion. [See G. Panayotou and W. D. Waterfield, 1993, Bioessays 15:171; M. Mohammadi et al., 1996, Cell 86:577

  • Figure 15-57. Some of the protein kinases discussed in this chapter. The tyrosine kinases shown are bound to the plasma membrane, whereas most of the serine/threonine kinases are in the cytosol.

  • Cytokines in the Immune system

  • STATs and SMADs: Linking receptors to transcription.Pawson T and Nash P (2000). Genes Dev.,1027

  • STAT= Signal Transducer and Activator of Transcription

  • Three examples of signaling in the JAK-STAT pathway. Specific ligand-receptor interactions generate active transcription complexes composed of distinct STAT proteins. GAS= gamma activated sequence

  • Variations in STAT activation mechanisms

  • Structural features of Src-kinases, JAKs and SOCS/CIS/JAB protein family proteins.