14.1: TGFB Receptors and the Direct Activation of Smads

• Inactive precursors produce TGFB and extracellular matrixes sore them.

• A dimeric growth factor can be released through mechanisms

• Intrinsic serine/threonine kinase can be released through TGFB which releases a nuclear-localized signal after R-Smad moves out of the way

• R-Smad binds to co-Smad, and that results in the created complex entering the nucleus

• The complex and transcription factors help with the expression of target genes

• Negative regulators of TGFB signaling

  • Oncoproteins

  • Ski

  • SnoN

  • I-Smads

  • Smad7

• Proliferation can be blocked due to TGFB signaling. If all the components needed are not present in the signaling pathway there can be abnormalities in the cell

14.2: Cytokine Receptors and the JAK-STAT Pathway

• Receptor classes create signals through their associated proteins

• Cytokine receptors

• Receptor tyrosine kinases

• Ligands trigger functional dimeric receptors and phosphorylation located in the lip in the kinases into a formation. This enhances the activity of catalysts.

• Cytokines characteristics

  • Four helices

  • Folded into a specific arrangement

• Erythropoietin helps to induce proliferation and differentiation of bone marrow erythroid progenitor cells, along with preventing apoptosis.

• Erythropoietin helps prevent down-regulation and elevated the number of blood cells

• JAK protein tyrosine kinase and cytokine receptors are associated with each other and JAK protein tyrosine kinase can send stream signaling which helps with the activity of proteins and the transcription of certain genes

• STAT monomers and JAKs aid in the activation of transcription by dimerizing and moving towards the nucleus of the cell

• STAT and JAK create a pathway that is downstream and comes into contact with all cytokine receptors. STAT is phosphorylated by JAKs dimerize, move to the nucleus, and activate transcription

• Peptide sequences with phosphotyrosine attach themselves to SH2 and PTB domains in signal-transducing proteins.

• Phosphotyrosine terminates signals from cytokine receptors.

14.3: Receptor Tyrosine Kinases and Activation of Ras

• Receptor Tyrosine Kinases

  • Bind to protein and peptide hormones

  • Exist as preformed dimers or

  • Dimerize when binding with ligands

• The activation of protein tyrosine activity of the receptor occurs through ligand binding, and the cytosolic domain of tyrosine is reduced through phosphorylation

• Ras is a type of GTPase protein that has similar downstream functions to RTKs

• Ras needs a guanine nucleotide exchange factor and GTPase activating protein for cycling

• Adapter protein GRB2 and Sos, associated with GEF activity, are both directly linked to RTKs

14.4: MAP Kinase Pathways

• Raf, MEK, and MAP are triggered through activated Ras, and the activated MAP kinase dimerizes and moved towards the nucleus.

• MAP kinase activation helps the activation and phosphorylation and TCF and SRF, which are transcription factors

• TCF and SRF promote the transcription of some early response genes

• MAP kinase pathways are found in yeast and higher eukaryotes and are triggered through the activation of receptors

• Different cellular processes occur depending on the type of MAP kinase that is activated through various signals

14.5: Phosphoinositides as Signal Transducers

• The IP3/AG pathway can be initiated by RTKs and Cytokine receptors.

• This is done through activating phospholipase PLCy

• Other phosphoinositide pathways can be initiated through activated RTKs by the binding of PI-3 kinases

• PI 3-phosphates are bonded through the PH domain of proteins, which helps to form signaling complexes in the plasma membrane

• Protein kinase B needs PI 3-phosphates and PDK1 to fully activate

• Protein kinase B helps with the survival of cells by presenting the actions of pro-apoptotic proteins

14.6: Pathways That Involve Signal-Induced Protein Cleavage

• NF-kB helps to regulate genes that tell cells to respond to infections and inflammation in the body

• NF-kB is located in the cytosol which is bound to an inhibitor protein called I-kB

• Degradation and ubiquitination of I-kB releases NF-kB which moves towards the nucleus

14.7: Down-Modulation of Receptor Signaling

• The sensitivity of hormones can be decreased through the number of receptor tyrosine kinases and cytokine receptors on the cell surface due to the receptor hormones degradation in lysosomes

• RANKL and RANK, its receptor, binding together results in bone resorption

• This fusion helps the release of HCI, a bone dissolving mixture, and the adhesion of osteoclasts to the bone

• DNA techniques can be produced by cell surface receptors and can be used as decoy receptors