Date of Award

1996

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biology

Abstract

Stathmin is a highly conserved, soluble, cytosolic, 19 kDa protein. It is phosphorylated in response to hormones, growth and differentiation factors, and neurotransmitters. Its function is unknown. It is phosphorylated by mitogen activated protein (MAP) kinase and p34$\sp{\rm cdc2}$ kinase in vitro and these kinases are suspected to phosphorylate stathmin in vivo. MAP kinase is activated in response to extracellular signals. It phosphorylates regulatory proteins involved with the initiation of transcription and translation. p34$\sp{\rm cdc2}$ kinase is a cyclin-dependent protein kinase. Its activation is required for cellular proliferation and it phosphorylates key regulatory proteins involved with cell cycle control. Stathmin genes were modified at MAP and p34$\sp{\rm cdc2}$ kinase phosphorylation sites, serine 25 and 38. Mutated stathmin genes were transfected into 3T3-F442A cells. Modification of the serine at position 38 to an alanine disrupted the ability of these cells to replicate DNA and proceed through mitosis in response to mitogenic signals. The mutation of serine to alanine at position 25 disrupted cellular morphology when the cells were exposed to differentiation factors. A rat homologue of mouse tumor DNA J-like (MTJ1; originally defined as IC47) protein was isolated as a prolactin (PRL) induced gene from Nb$\sb2$ cells. Reverse-transcriptase polymerase chain reaction was used to demonstrated that this gene was not upregulated in Nb$\sb2$ cells in response to PRL up to 8 hr or in 3T3 F442A in response to the differentiation agent insulin after 8 hr of exposure.

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