Gwendolyn Quintana 01187235 04 16 13 1 How do cells prevent crosstalk between kinase pathways i e once In a real situation cross talk is common to most cells commonly by cross talk using cross presentation of proteins within signal transduction cascades Many times phosphorylation and G coupled proteins are ligand specific or have cAMP requirements that can distinguish the specific amplification of a phosphorylation cascade molecule as opposed to a neighboring signal transduction cascade 2 Compare Ras and the G proteins as to activation inactivation by GTP In the off state Ras is bound to GDP In the on state Ras is bound to GTP Ras is a G protein and can be phosphorylated Regulation of g proteins in the active state the alpha subunit is bound to the GDP in a complex with beta and hormone binding stimulates the release of GDP and its exchange for GTP The activated bound GTP alpha subunit and other subunit then dissociates from the receptor and interacts with the receptor and their target Activity of the alpha subunit is terminated by hydrolysis of GTP and the inactive GDP bound alpha subunit then reassociates with the beta complex Ras is converted to the active GTP bound state by exchange of GTP for bound DP which is stimulated by guanine nucleotide exchange factors GEFs Ras activity is then terminated by GTP hydrolysis which is stimulated by GTPase activating proteins GAPs 3 In human cancer is the Ras protein activity enhanced or inhibited Explain In human cancer the Ras protein activity is enhanced Ras Raf lies upstream to kinase pathways such as ERK ERK part of an evolutionarily conserved pathway that regulates cell differentiation cell survival and cell proliferation Hence in the upregulation of Ras Raf there is an increase in cell differentiation survival and cell proliferation 4 What relationship association or similarity does Ras have to PI 3 kinase Extracellular ligands such as growth factors GF or insulin bind receptors that activate signal transduction pathways involving Ras and PI 3 kinase PI 3 K They both lie on the same pathway PI 3 K is downstream of Ras Likewise they are both kinases and elicit the continuation of a phosphorylation cascade upon signal recognition They are both involved in the MAPK signal transduction pathway 5 G0 cell cycle arrest M mitosis G1 interval between mitosis and DNA replication cell growth S DNA replication G2 cell growth continues and proteins synthesized in preparation for mitosis 6 Cyclin B synthesized and complexes with existing Cdk1 during G2 Cdk1 phosphorylaiton at Thr 161 is required for activity and also phosphorylated at Try 15 and Thr 14 which inhibits action by Cdk1 complex during G2 M phase initiated by Cdc25C phosphatase that dephosphorylates Cdk1 Cdk1 cyclin act 1 M phase 2 triggers degradation cyclin B via Ubiquination 7 Compare normal adult cell mitosis and embryonic cell mitosis In adult cells there are all stages of mitosis In embryonic cells there is G1 and G2 lacking with a short S and M phase 8 MCM helicase only bind in G1 to replication origins together with ORC proteins following DNA replication beginning in phase MCM gets displaced to ensure DNA replication cannot occur 9 Define cell cycle checkpoints G2 unreplicated of damagen DNA in M chromosome misalignment spindle assembly checkpoint In S unreplicated or damaged DNA in G1 damaged DNA 10 List the different kinds of microtubules and give the function of each in the cell cycle There are astral kinetochore chromosomal and polar microtubules Astral microtubules originate from the centrosome and don t connect to a kinetochore they make the actin skeleton and interact with the cell cortex to aid in spindle orientation Kinetochore microtubules are on the chromatids where the spindle fibers attach during cell division to pull sister chromatids apart Chromosomal microtubules do not attach to define kinetochores but in all stages extend all the way from the chromatin to the pole Polar microtubules are used with molecular motors and are attached to a microtubule from either side at the place where the polar microtubules overlap During metaphase and anaphase the motors push the microtubules away in opposite directions As this happens the microtubules polymerize and get longer The result is an elongation of the cell http faculty plattsburgh edu donald slish Motors html